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Article in English | WPRIM | ID: wpr-878349


Objective@#To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2 (LMP2) modified dendritic cells (DCs) that boosts specific responses of cytotoxic T lymphocytes (CTLs) to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma (NPC).@*Methods@#DCs were derived from peripheral blood monocytes of patients with NPC. We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2 (rAd-LMP2). NPC patients were immunized with 2 × 10 @*Results@#We demonstrated that DCs derived from monocytes displayed typical DC morphologies; the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay. Twenty-nine patients with NPC were enrolled in this clinical trial. The LMP2-DCs vaccine was well tolerated in all of the patients. Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC. The follow-up data of 29 immunized patients from April, 2010 to April 2015 indicated a five-year survival rate of 94.4% in responders and 45.5% in non-responders.@*Conclusion@#In this pilot study, we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC. Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC, which warrants further clinical testing.

Adult , Aged , Cancer Vaccines/therapeutic use , China , Dendritic Cells/immunology , Female , Humans , Immunotherapy/methods , Injections, Intradermal , Male , Middle Aged , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Neoplasms/therapy , T-Lymphocytes, Cytotoxic/immunology , Viral Matrix Proteins/therapeutic use , Young Adult
Rev. méd. Chile ; 146(2): 150-159, feb. 2018. tab, graf
Article in English | LILACS | ID: biblio-961372


ABSTRACT Background: The dual potential to promote tolerance or inflammation when facing self-antigens makes dendritic cells (DCs) fundamental players in autoimmunity. There is an association between smoking and DCs maturation in patients with rheumatoid arthritis (RA). However, ethnicity is a key factor in autoimmune disorders. Aim: To evaluate phenotypic and functional alterations of DCs obtained from Chilean patients with RA as compared to healthy controls (HC). In second term, to compare the inflammatory behaviour of DCs between smoker and non-smoker patients. Material and Methods: Monocyte-derived DCs and T-cells were obtained from blood samples isolated from 30 HC and 32 RA-patients, 14 of which were currently smokers and 18 non-smokers. Several maturation surface markers were evaluated in DCs, including HLA-DR, CD40, CD80, CD83 and CD86. Furthermore, autologous co-cultures of DCs and T-cells were carried out and then T-cell proliferation, and expansion of Th1, Th17 and Tregs were analysed. Results: Compared with HC, RA-patients displayed increased HLA-DR expression in DCs, which was manifested mainly in patients with moderate-to- high disease activity scores (DAS28). Furthermore, RA-patients presented a stronger Th17-expansion and a correlation between DAS28 and Th1-expansion. Both effects were mainly observed in patients in remission or with a low DAS28. Moreover, smoker RA-patients displayed enhanced HLA-DR and CD83 expression in DCs as well as an exacerbated Th17-expansion and a correlation between DAS28 and Th1-expansion. Conclusions: These findings suggest that smoking enhances the inflammatory behaviour of DCs and the consequent Th1 and Th17-mediated response in patients with RA

Introducción: El potencial dual que poseen para promover tolerancia o inflamación ante antígenos propios, hace de las células dendríticas (CDs) actores fundamentales en el desarrollo de autoinmunidad. Existe una asociación entre fumar y la maduración de las CDs en pacientes con artritis reumatoide (AR). No obstante, la etnicidad es un factor clave a considerar en desórdenes autoinmunes. Objetivos: Comparar las alteraciones fenotípicas y funcionales de las CDs obtenidas desde pacientes Chilenos con AR y controles sanos (CS). Además, analizamos las diferencias en el comportamiento inflamatorio que existe entre las CDs obtenidas de pacientes fumadores y CS. Materiales y Métodos: Se obtuvieron CDs derivadas de monocitos y células T desde muestras de sangre aisladas de 30 CS y 32 pacientes con AR, 14 de los cuales eran fumadores y 18 no fumadores. Se evaluaron marcadores de maduración en la superficie de las CDs: HLA-DR, CD40, CD80, CD83 y CD86. Además, se realizaron co-cultivos autólogos de células T y CDs, analizando la proliferación de células T, y la expansión de células Th1, Th17 y Tregs. Resultados: En comparación con los CS, los pacientes AR mostraron un aumento de la expresión de HLA-DR en las CDs, principalmente en los individuos con DAS28 moderado-alto. Los pacientes con AR presentaron una mayor expansión de células Th17 y una correlación entre el DAS28 y la expansión de células Th1, ambos efectos manifestados principalmente en los individuos con un DAS28 bajo o en remisión. Además, los pacientes con AR fumadores mostraron un aumento en la expresión de HLA-DR y CD83 en las CDs y una expansión de células Th17 exacerbada así como una correlación entre el DAS28 y la expansión de células Th1. Conclusiones: Nuestros resultados sugieren que fumar favorece el comportamiento inflamatorio de las CDs y en consecuencia la inducción de respuestas mediadas por células Th1 y Th17 en los pacientes Chilenos con AR.

Humans , Female , Middle Aged , Arthritis, Rheumatoid/metabolism , Dendritic Cells/immunology , Smoking/adverse effects , Cell Proliferation/physiology , Phenotype , Arthritis, Rheumatoid/physiopathology , Arthritis, Rheumatoid/immunology , Smoking/physiopathology , Antigens, Differentiation, B-Lymphocyte/immunology , HLA-DR Antigens/immunology , Case-Control Studies , Chile , T-Lymphocyte Subsets/immunology , Disease Progression , Flow Cytometry , Inflammation/physiopathology , Inflammation/drug therapy
Braz. oral res. (Online) ; 32(supl.1): e71, 2018. graf
Article in English | LILACS | ID: biblio-974472


Abstract: The purpose of this manuscript was to re-discuss apical periodontitis, apical biofilm, and its possible relationship with dendritic cells (DC). DCs are potent regulators of the immune system and their function is divided into three categories that involve the presentation of antigens: the presentation of antigens and activation of T cells; a not well established category suggested that DCs induce and maintain immunological tolerance; and the maintenance of the immune memory in conjunction with B cells. DCs in periapical inflammatory lesions are composed of at least two subpopulations that can be distinguished on the basis of ultrastructure and phenotype. These populations might differ in lineage, state of maturation, differentiation, activation, and/or function. The authors hereby analyzed the root apexes of teeth under SEM, after performing apicoectomy due to the failure of conventional endodontic treatment. Microbial biofilm with multispecies and areas of resorption with the presence of Howship lacunae, and images suggestive of denditric cells could be observed. The presence of DCs in periapical lesion could be an indication of the severity of the lesion, with a constant presence of antigen in the periradicular region.

Humans , Periapical Periodontitis/microbiology , Periapical Periodontitis/pathology , Dendritic Cells/pathology , Biofilms , Periapical Periodontitis/immunology , Dendritic Cells/immunology , Microscopy, Electron, Scanning , T-Lymphocytes/immunology , T-Lymphocytes/microbiology , Antigens/immunology
Int. braz. j. urol ; 43(4): 615-627, July-Aug. 2017. tab, graf
Article in English | LILACS | ID: biblio-892856


ABSTRACT Background In order to induce a potent cytotoxic T lymphocyte (CTL) response in dendritic cell (DC)-based immunotherapy for bladder cancer, various tumor antigens can be loaded onto DCs. Objective The aim of this study was to establish a method of immunotherapy for male patients with non-muscle invasive bladder cancer (NMIBC), using bladder cancer-specific CTLs generated in vitro by DCs. Materials and Methods Monocyte-derived DCs from bladder cancer patients were induced to mature in a standard cytokine cocktail (IL-1β, TNF-α, IL-6, and PGE2: standard DCs, sDCs) or anα-type 1-polarized DC (αDC1) cocktail (IL-1β, TNF-α, IFN-α, IFN-γ, and polyinosinic:polycytidylic acid) and loaded with the UVB-irradiated bladder cancer cell line, T24. Antigen-loaded αDC1s were evaluated by morphological and functional assays, and the bladder cancer-specific CTL response was analyzed by cytotoxic assay. Results The αDC1s significantly increased the expression of several molecules pertaining to DC maturation, regardless of whether or not the αDC1s were loaded with tumor antigens, relative to sDCs. The αDC1s demonstrated increased production of interleukin-12 both during maturation and after subsequent stimulation with CD40L that was not significantly affected by loading with tumor antigens as compared to that of sDCs. Bladder cancer-specific CTLs targeting autologous bladder cancer cells were successfully induced by αDC1s loaded with dying T24 cells. Conclusion Autologous αDC1s loaded with an allogeneic bladder cancer cell line resulted in increased bladder cancer-specific CTL responses as compared to that with sDCs, and therefore, may provide a novel source of DC-based vaccines that canbe used in immunotherapy for male patients with NMIBC.

Humans , Male , Aged , Urinary Bladder Neoplasms/therapy , Dendritic Cells/immunology , T-Lymphocytes, Cytotoxic/immunology , Cytokines/therapeutic use , Immunotherapy/methods , Urinary Bladder Neoplasms/immunology , Cell Differentiation/immunology , Treatment Outcome , Cell Line, Tumor , Immunotherapy/adverse effects , Middle Aged
Rev. chil. infectol ; 34(3): 249-256, jun. 2017. ilus, tab
Article in Spanish | LILACS | ID: biblio-899708


Dengue fever, caused by dengue virus (DENV) infection, is one of the most important diseases in the world, not only due to the high morbidity/mortality rates it causes, but also because of its great economic and social impact in tropical/subtropical countries. DENV infection has a wide range of clinical manifestations ranging from asymptomatic infection or infection with mild symptoms to severe dengue that can lead to death. At present, no etiological treatment or effective globally distributed vaccine against the four DENV serotypes exists. Despite great efforts made to understand the mechanism associated with DENV disease pathogenesis the causes leading to severe dengue presentation have not been clarified. Some hypotheses seek to give a biological and physiological explanation to the clinical manifestations that appear during the infection. Based on the evidence that after contact with dendritic cells DENV alters the functionality of these cells, this review aims to describe the most relevant findings regarding the importance of dendritic cells in the context of DENV infection and progression of the illness.

El dengue, causada por el virus dengue (DENV), es una de las enfermedades más importantes no sólo por los altos índices de morbilidad/mortalidad, sino también por su gran impacto económico y social en los países de las regiones tropicales/subtropicales. La infección por el DENV cursa por un variado rango de manifestaciones clínicas que van desde una infección asintomática o con síntomas leves, hasta el dengue grave que puede ser fatal. En la actualidad, no se dispone de un tratamiento etiológico y tampoco de una vacuna eficaz mundialmente distribuida, contra los 4 serotipos del DENV. A pesar de los grandes esfuerzos orientados a entender el mecanismo asociado con la patogénesis de la enfermedad, aún no se ha logrado esclarecer de forma definitiva las causas que conllevan a las formas graves de enfermedad. Algunas hipótesis buscan dar una explicación biológica y fisiológica a las manifestaciones clínicas que se presentan durante la infección. Dado que una de ellas sugiere que luego del contacto con las células dendríticas el DENV altera su funcionalidad, la presente revisión tiene como objetivo describir los hallazgos más relevantes referentes a la importancia de dichas células en el marco de la infección por el DENV y progresión de la enfermedad.

Humans , Virus Replication/immunology , Dendritic Cells/immunology , Dengue/immunology , Dengue Virus/immunology , Disease Progression , Immunity, Cellular , Immunity, Innate
Article in English | WPRIM | ID: wpr-216444


Cervical cancer is the fourth most lethal women's cancer worldwide. Current treatments against cervical cancer include surgery, radiotherapy, chemotherapy, and anti-angiogenic agents. However, despite the various treatments utilized for the treatment of cervical cancer, its disease burden remains a global issue. Persistent infection of human papillomavirus (HPV) has been identified as an essential step of pathogenesis of cervical cancer and many other cancers, and nation-wide HPV screening as well as preventative HPV vaccination program have been introduced globally. However, even though the commercially available prophylactic HPV vaccines, Gardasil (Merck) and Cervarix (GlaxoSmithKline), are effective in blocking the entry of HPV into the epithelium of cervix through generation of HPV-specific neutralizing antibodies, they cannot eliminate the pre-existing HPV infection. For these reason, other immunotherapeutic options against HPV-associated diseases, including therapeutic vaccines, have been continuously explored. Therapeutic HPV vaccines enhance cell-mediated immunity targeting HPV E6 and E7 antigens by modulating primarily dendritic cells and cytotoxic T lymphocyte. Our review will cover various therapeutic vaccines in development for the treatment of HPV-associated lesions and cancers. Furthermore, we will discuss the potential of immune checkpoint inhibitors that have recently been adopted and tested for their treatment efficacy against HPV-induced cervical cancer.

Dendritic Cells/immunology , Female , Genetic Vectors , Humans , Immunotherapy , Papillomavirus Infections/complications , Papillomavirus Vaccines/therapeutic use , Translational Medical Research , Uterine Cervical Neoplasms/therapy , Vaccines, DNA/therapeutic use , Vaccines, Subunit/therapeutic use
J. appl. oral sci ; 23(5): 536-546, Sept.-Oct. 2015. tab, graf
Article in English | LILACS | ID: lil-764159


In Aggregatibacter actinomycetemcomitans, different serotypes have been described based on LPS antigenicity. Recently, our research group has reported a differential immunogenicity when T lymphocytes were stimulated with these different serotypes. In particular, it was demonstrated that the serotype b of A. actinomycetemcomitans has a stronger capacity to trigger Th1- and Th17-type cytokine production.Objective This study aimed to quantify the expression of different CC chemokines (CCLs) and receptors (CCRs) in T lymphocytes stimulated with the differentA. actinomycetemcomitans serotypes. In addition, the expression of the transcription factors T-bet, GATA-3, RORC2, and Foxp3, master-switch genes implied in the Th1, Th2, Th17, and T-regulatory differentiation, respectively, was analysed in order to determine T-cell phenotype-specific patterns of CCL and CCR expression upon A. actinomycetemcomitans stimulation.Material and Methods Human naïve CD4+ T lymphocytes were obtained from healthy subjects and stimulated with autologous dendritic cells primed with the differentA. actinomycetemcomitans serotypes. The expression levels for the chemokines CCL1, CCL2, CCL3, CCL5, CCL11, CCL17, CCL20, CCL21, CCL25, and CCL28, as well as the chemokine receptors CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 were quantified by qPCR. Similarly, the expression levels for the transcription factors T-bet, GATA-3, RORC2, and Foxp3 were quantified and correlated with the CCL and CCR expression levels.Results Higher expression levels of CCL2, CCL3, CCL5, CCL20, CCL21, CCL28, CCR1, CCR2, CCR5, CCR6, CCR7, and CCR9 were detected in T lymphocytes stimulated with the serotype b of A. actinomycetemcomitans compared with the other serotypes. In addition, these higher expression levels of CCLs and CCRs positively correlated with the increased levels of T-bet and RORC2 when T lymphocytes were stimulated with the serotype b.Conclusion A T-lymphocyte response biased towards a Th1- and Th17-pattern of CCL and CCR expression was detected under stimulation with the serotype b ofA. actinomycetemcomitans.

Adult , Female , Humans , Male , Young Adult , Aggregatibacter actinomycetemcomitans/immunology , Antigens, Differentiation, T-Lymphocyte/analysis , Chemokines, CC/analysis , Receptors, CCR/analysis , T-Lymphocytes/immunology , Aggregatibacter actinomycetemcomitans/genetics , Antigens, Differentiation, T-Lymphocyte/genetics , Antigens, Differentiation, T-Lymphocyte/immunology , Cells, Cultured , Cell Differentiation/immunology , Chemokines, CC/genetics , Chemokines, CC/immunology , Dendritic Cells/immunology , Flow Cytometry , Lymphocyte Activation , Polymerase Chain Reaction , Receptors, CCR/genetics , Receptors, CCR/immunology , Serogroup
Rev. peru. med. exp. salud publica ; 32(3): 555-564, jul.-sep. 2015. ilus
Article in Spanish | LILACS, LIPECS, INS-PERU | ID: lil-790744


La presente es una revisión narrativa que muestra la información accesible a la comunidad científica sobre melanoma e inmunoterapia. Las células dendríticas tienen la capacidad de participar en la inmunidad innata y adaptativa, pero no son ajenas a la evasión inmune de los tumores. Conocer su biología y rol ha llevado a generar in vitro varios prospectos de vacunas celulares autólogas contra diversos tipos de cáncer en humanos y modelos animales; sin embargo, en vista de la poca eficiencia que han mostrado, se deben implementar estrategias para potenciar su capacidad natural ya sea a través de la coexpresión de moléculas clave para activar o reactivar al sistema inmune, en combinación con biosimilares o drogas quimioterapeúticas y no se debe descartar la acción de productos naturales como alternativa inmunoestimulante o adyuvante. Todos los tipos de inmunoterapía deberían medir el impacto de las células supresoras de origen mieloide, las que pueden atacar al sistema inmune y ayudar a la progresión tumoral, respectivamente. Esto puede reducir la actividad de las vacunas celulares y/o sus combinaciones pudiendo ser la diferencia entre el éxito o no de la inmunoterapia. Aunque en melanoma existen biosimilares aprobados por la Food and Drug Administration (FDA) no todos tienen el éxito esperado por lo que es necesario evaluar otras estrategias que incluyan vacunas celulares cargadas con péptidos antigénicos tumorales expresados exclusivamente o antígenos provenientes de extractos tumorales y sus respectivos adyuvantes...

This is a narrative review that shows accessible information to the scientific community about melanoma and immunotherapy. Dendritic cells have the ability to participate in innate and adaptive immunity, but are not unfamiliar to the immune evasion of tumors. Knowing the biology and role has led to generate in vitro several prospects of autologous cell vaccines against diverse types of cancer in humans and animal models. However, given the low efficiency they have shown, we must implement strategies to enhance their natural capacity either through the coexpression of key molecules to activate or reactivate the immune system, in combination with biosimilars or chemotherapeutic drugs. The action of natural products as alternative or adjuvant immunostimulant should not be ruled out. All types of immunotherapy should measure the impact of myeloid suppressor cells, which can attack the immune system and help tumor progression, respectively. This can reduce the activity of cellular vaccines and/or their combinations, that could be the difference between success or not of the immunotherapy. Although for melanoma there exist biosimilars approved by the Food and Drug Administration (FDA), not all have the expected success. Therefore it is necessary to evaluate other strategies including cellular vaccines loaded with tumor antigenic peptides expressed exclusively or antigens from tumor extracts and their respective adjuvants...

Humans , Dendritic Cells/immunology , Immunotherapy , Melanoma , Cat's Claw/immunology , Vaccines
Mem. Inst. Oswaldo Cruz ; 110(5): 655-661, Aug. 2015. ilus
Article in English | LILACS | ID: lil-755889


Dendritic cells (DCs) play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. Studies on the interaction of monocyte-derived DCs (MO-DCs) using Mycobacterium leprae in leprosy patients are rare. The present study demonstrated that the differentiation of MOs to DCs was similar in all forms of leprosy compared to normal healthy individuals. In vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable degrees of DC maturation as determined by the increased expression of HLA-DR, CD40, CD80 and CD86, but not CD83, in all studied groups. The production of different cytokines by the MO-DCs appeared similar in all of the studied groups under similar conditions. However, the production of interleukin (IL)-12p70 by MO-DCs from lepromatous (LL) leprosy patients after in vitro stimulation with M. lepraewas lower than tuberculoid leprosy patients and healthy individuals, even after CD40 ligation with CD40 ligand-transfected cells. The present cumulative findings suggest that the MO-DCs of LL patients are generally a weak producer of IL-12p70 despite the moderate activating properties ofM. leprae. These results may explain the poor M. leprae-specific cell-mediated immunity in the LL type of leprosy.


Female , Humans , Male , Cytokines/biosynthesis , Dendritic Cells/immunology , Leprosy, Lepromatous/immunology , Monocytes/immunology , Mycobacterium leprae/immunology , Antigens, Bacterial/immunology , Case-Control Studies , In Vitro Techniques , /immunology , Retrospective Studies
Ciênc. saúde coletiva ; 20(1): 85-94, 01/2015. tab
Article in Portuguese | LILACS | ID: lil-733143


O presente estudo propõe-se a identificar a prevalência do acesso a informações sobre como evitar problemas bucais entre escolares da rede pública de ensino, assim como os fatores associados a este acesso. Trata-se de um estudo transversal e analítico conduzido entre escolares de 12 anos de idade de um município brasileiro de grande porte populacional. Os exames foram realizados por 24 cirurgiões-dentistas treinados e calibrados com auxilio de 24 anotadores. A coleta de dados ocorreu em 36 escolas sorteadas das 89 escolas públicas do município. Foram conduzidas análises descritivas, univariadas e múltiplas. Dos 2510 escolares incluídos no estudo, 2211 relataram já ter recebido informações sobre como evitar problemas bucais. O acesso a tais informações foi maior entre os que utilizaram serviços odontológicos privado/convênio; e menor entre aqueles que utilizaram o serviço para tratamento, os que avaliaram o serviço como regular ou ruim/péssimo, os que utilizam como meio de higiene bucal somente escova dente/escova dente e higienização a língua e os que relataram não estarem satisfeitos com a aparência de seus dentes. Conclui-se que a maioria dos escolares teve acesso a informações sobre como evitar problemas bucais, o qual esteve associado a características dos serviços de saúde, comportamentos e desfechos de saúde.

The scope of this study is to identify the prevalence of access to information about how to prevent oral problems among schoolchildren in the public school network, as well as the factors associated with such access. This is a cross-sectional and analytical study conducted among 12-year-old schoolchildren in a Brazilian municipality with a large population. The examinations were performed by 24 trained dentists and calibrated with the aid of 24 recorders. Data collection occurred in 36 public schools selected from the 89 public schools of the city. Descriptive, univariate and multiple analyses were conducted. Of the 2510 schoolchildren included in the study, 2211 reported having received information about how to prevent oral problems. Access to such information was greater among those who used private dental services; and lower among those who used the service for treatment, who evaluated the service as regular or bad/awful. The latter use toothbrush only or toothbrush and tongue scrubbing as a means of oral hygiene and who reported not being satisfied with the appearance of their teeth. The conclusion drawn is that the majority of schoolchildren had access to information about how to prevent oral problems, though access was associated with the characteristics of health services, health behavior and outcomes.

Animals , Humans , Mice , Autoimmune Diseases/immunology , Autoimmunity/immunology , Mast Cells/immunology , Multiple Sclerosis/immunology , Central Nervous System/immunology , Dendritic Cells/immunology , Self Tolerance , T-Lymphocytes/immunology
Salvador; s.n; 2015. 61 p. ilus.
Thesis in Portuguese | LILACS | ID: biblio-1000970


Os neutrófilos são essenciais para a resposta imune inata contra uma variedade de patógenos. Eles são capazes de modular a resposta imune através da produção de citocinas e quimiocinas, degranulação e a sua interação direta com outras células no local da infecção, tais como as células dendríticas. A interação entre as células do sistema imune inato é essencial para direcionar a resposta imune adaptativa, a qual é responsável pela eliminação de microrganismos e manutenção de memória imunológica. Objetivo: Este estudo avaliou a interação de neutrófilos humanos com Leishmania braziliensis, através da análise da expressão de moléculas de superfície, liberação de enzimas presentes nos grânulos e produção de espécies reativas de oxigênio (ROS). Também foi avaliada a interação entre neutrófilos humanos infectados e células dendríticas, a fim de se observar o efeito desta interação na indução da ativação das células dendríticas. Metodologia: Os neutrófilos foram purificados a partir do sangue periférico de doadores saudáveis e as células dendríticas foram geradas in vitro. Os neutrófilos foram infectados ou não com L. braziliensis e co-cultivados com as células dendríticas. Em seguida, os sobrenadantes e as células foram coletadas para avaliar a liberação de enzimas, tais como mieloperoxidase (MPO) e metaloproteinase 9 (MMP-9). O fenótipo e a função dos neutrófilos foram analisados através da expressão de Mac-1 (CD18 e CD11b), CD16, CD62-L e produção de ROS...

Neutrophils are essential in the innate immune response against a variety of pathogens. They are able to modulate immune response by cytokine and chemokine production, release of granules and their direct interaction with other cells at the infection site. Dendritic cells are recruited in response to cytokines and chemokines produced by neutrophils. The interaction between cells of the innate immune system is essential for targeting the adaptive immune response, which is responsible for eliminating microorganisms and the maintenance of immunological memory. Objective: Evaluate the interaction of human neutrophils with Leishmania braziliensis, through the analysis of surface molecule expression, release of granules enzymes and production of reactive oxygen species (ROS). We also evaluated the interaction between human infected neutrophils and dendritic cells, in order to observe the effect of this interaction on dendritic cells. Methodology: Neutrophils were purified from peripheral blood of healthy donors and dendritic cells were generated in vitro. Neutrophils were infected or not with L. braziliensis and cocultured with DC. Afterwards, supernatants and cells were harvested to evaluate the release of granules enzymes, such as myeloperoxidase (MPO) and metalloproteinase 9 (MMP-9). Neutrophils phenotype and function were analyzed by the expression of Mac-1 (CD18 and CD11b), CD16 and ROS production...

Humans , Dendritic Cells/cytology , Dendritic Cells/immunology , Dendritic Cells/pathology , Leishmania braziliensis/growth & development , Leishmania braziliensis/immunology , Leishmania braziliensis/parasitology , Leishmania braziliensis/pathogenicity , Neutrophils/immunology , Neutrophils/parasitology , Neutrophils/pathology
Indian J Cancer ; 2014 Jul-Sep; 51(3): 338-341
Article in English | IMSEAR | ID: sea-154405


Objective: The clinical outcome, especial the immunologic responses to cancer and graft, of dendritic cell (DC) vaccine in the treatment of advanced de novo colorectal cancer (CRC) in renal transplant patients was investigated in this study. Materials and Methods: 7 patients were received 1 cycle tumor lysate pulsed autologous DC vaccine. The positive cell-mediated cytotoxicity responses to DC vaccine against CRC cell in two out of 7 patients were seen by delayed type hypersensitivity (DTH) test. The positive cell-mediated cytotoxicity responses to DC vaccine against normal kidney cell in all 7 patients were not seen by DTH tests and no notable change of renal function during and after vaccination. Conclusions: DC vaccine has emerged as a promising new strategy in the treatment of advanced de novo CRC in renal transplant patients and DC vaccines have become an attractive therapeutic option, developing immune responses specific against CRC cell, achieving clinical efficacy without graft failure.

Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/etiology , Dendritic Cells/immunology , Humans , Kidney Transplantation/adverse effects , Tissue Donors , Vaccines/therapeutic use
An. bras. dermatol ; 89(4): 632-637, Jul-Aug/2014. tab, graf
Article in English | LILACS | ID: lil-715521


The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease.

Female , Humans , Male , Young Adult , Dendritic Cells/pathology , Graft vs Host Disease/pathology , Hematopoietic Stem Cell Transplantation , Killer Cells, Natural/pathology , Mouth Mucosa/pathology , Apoptosis , Antigens, CD/immunology , Biopsy , Cell Count , Chronic Disease , Dendritic Cells/immunology , Graft vs Host Disease/immunology , Immunohistochemistry , Killer Cells, Natural/immunology , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/pathology , Mouth Mucosa/immunology , Statistics, Nonparametric
Salvador; s.n; 2014. 83 p. ilus, tab.
Thesis in Portuguese | LILACS | ID: biblio-1000988


As alergias afetam cerca de 20 a 30% da população mundial e sua prevalência, bem como a gravidade dos sintomas, tem aumentado nas últimas décadas. As terapias existentes para as desordens do trato respiratório ocorrem por períodos prolongados, apresentam efeitos colaterais, muitas vezes não são efetivas para pacientes graves e dependem do afastamento do alérgeno. Uma alternativa para esses pacientes seria a indução de tolerância imunológica, através da terapia celular com células dendríticas pulsadas com o alérgeno. O presente trabalho objetivou avaliar o efeito de células dendríticas mielóides sensibilizadas in vitro com extrato de B. tropicalis em modelo murino de alergia respiratória. Em modelos experimentais de alergia respiratória, células T auxiliares (Th2)...

Allergies affect about 20-30% of world population and its prevalence and severity of symptoms has increased in recent decades. Existing therapies to respiratory tract disorders are extense, with side effects, not effective for severe patients and depending on the allergen removal. An alternative for these patients is the induction of immune tolerance by cell therapy with dendritic cells pulsed with the allergen. This study aimed to evaluate the effect of myeloid dendritic cells sensitized in vitro with B. tropicalis extract in a murine model of respiratory allergy. In experimental models of respiratory allergy, T helper cells (Th2)...

Humans , Dendritic Cells/immunology , Dendritic Cells/pathology , Immune Tolerance , Immune Tolerance/immunology , Mites/immunology
Article in English | WPRIM | ID: wpr-161403


Dendritic cells (DCs) are key modulators that shape the immune system. In mucosal tissues, DCs act as surveillance systems to sense infection and also function as professional antigen-presenting cells that stimulate the differentiation of naive T and B cells. On the basis of their molecular expression, DCs can be divided into several subsets with unique functions. In this review, we focus on intestinal DC subsets and their function in bridging the innate signaling and adaptive immune systems to maintain the homeostasis of the intestinal immune environment. We also review the current strategies for manipulating mucosal DCs for the development of efficient mucosal vaccines to protect against infectious diseases.

Animals , Dendritic Cells/immunology , Humans , Immunity, Mucosal , Intestinal Mucosa/cytology , T-Lymphocytes, Helper-Inducer/immunology
Yonsei Medical Journal ; : 1014-1027, 2014.
Article in English | WPRIM | ID: wpr-113973


PURPOSE: Vaccine strategies utilizing dendritic cells (DCs) to elicit anti-tumor immunity are the subject of intense research. Although we have shown that DCs pulsed with heat-treated tumor lysate (HTL) induced more potent anti-tumor immunity than DCs pulsed with conventional tumor lysate (TL), the underlying molecular mechanism is unclear. In order to explore the molecular basis of this approach and to identify potential antigenic peptides from pancreatic cancer, we analyzed and compared the major histocompatibility complex (MHC) ligands derived from TL- and HTL-pulsed dendritic cells by mass spectrophotometry. MATERIALS AND METHODS: Human monocyte-derived dendritic cells were pulsed with TL or HTL prior to maturation induction. To delineate differences of MHC-bound peptide repertoire eluted from DCs pulsed with TL or HTL, nanoflow liquid chromatography-electrospray ionization-tandem mass spectrometry (nLC-ESI-MS-MS) was employed. RESULTS: HTL, but not TL, significantly induced DC function, assessed by phenotypic maturation, allostimulation capacity and IFN-gamma secretion by stimulated allogeneic T cells. DCs pulsed with TL or HTL displayed pancreas or pancreatic cancer-related peptides in context of MHC class I and II molecules. Some of the identified peptides had not been previously reported as expressed in pancreatic cancer or cancer of other tissue types. CONCLUSION: Our partial lists of MHC-associated peptides revealed the differences between peptide profiles eluted from HTL-and TL-loaded DCs, implying that induced heat shock proteins in HTL chaperone tumor-derived peptides enhanced their delivery to DCs and promoted cross-presentation by DC. These findings may aid in identifying novel tumor antigens or biomarkers and in designing future vaccination strategies.

Antigens, Neoplasm/immunology , Cell Line, Tumor , Dendritic Cells/immunology , Humans , Pancreatic Neoplasms/immunology
West Indian med. j ; 62(9): 787-792, Dec. 2013. ilus, graf
Article in English | LILACS | ID: biblio-1045757


OBJECTIVE: This study aims to explore the chemokine receptor 7 (CCR7) expression of spleen dendritic cells (DCs) and their role in the changes of migration and activity of spleen DCs in multiple-organ dysfunction syndrome (MODS). METHODS: The MODS model of mice was reproduced. The mice were randomly assigned to the following groups: normal, three-hour to six-hour, 24-hour to 48-hour, and 10-day to 12-day postzymosan injection. CD11c and CD205 were analysed by immunohistochemistry; the expressions of CD86 and CCR7 of DCs were studied using flow cytometry analyses. RESULTS: In normal mice, many DCs were found at the margin between the red and white pulp. In the three-hour to six-hour and 24- to 48-hour group, DC effectively upregulated CD86 and CCR7, and they were distributed in T-cell areas. In the 10-day to 12-day group, DCs were distributed at the margin by the immature form. CONCLUSION: The CCR7 expression level of DCs had close correlations with the migration of DCs. Chemokine receptor 7 can be used to evaluate the migration and functional activity of DCs in MODS.

OBJETIVO: Este estudio persigue explorar la expresión del receptor de la quimiocina 7 (CCR7) de células dendríticas del bazo (CD), y su papel en los cambios de la migración y la actividad del las células DC del bazo en el síndrome de disfunción orgánica múltiple (SDOM). MÉTODOS: Se reprodujo el modelo SDOM de los ratones. Los ratones fueron asignados aleatoriamente a los siguientes grupos de inyección de post-zymosan: hora normal, tres a seis horas, 24 horas a 48 horas, y de 10 a 12 días. CD11c y CD205 fueron analizados mediante inmunohistoquímica. Las expresiones de CD86 y CCR7 de CD se estudiaron mediante análisis de citometría de flujo. RESULTADOS: En los ratones normales, muchas células CD fueron encontradas en el margen entre la pulpa roja y la blanca. En el grupo de tres a seis horas y el grupo de 24 a 48 horas, CD86y CCR7 fueron efectivamente sobre-regulados en CD, y distribuidos en las áreas de células T. En el grupo de 10 a 12 días, las CDs fueron distribuidas en el margen por la forma inmadura. CONCLUSIÓN: El nivel de expresión CCR7 de las CDs tuvo estrecha correlación con la migración de las CDs. El receptor de la quimiocina de tipo 7 puede utilizarse para evaluar la migración y la actividad funcional de las CDs en SDOM.

Animals , Male , Mice , Spleen/cytology , Dendritic Cells/immunology , Receptors, Chemokine/immunology , Multiple Organ Failure/pathology , Immunohistochemistry , Cell Movement , Disease Models, Animal , Mice, Inbred C57BL , Multiple Organ Failure/immunology
Mem. Inst. Oswaldo Cruz ; 108(6): 691-698, set. 2013. graf
Article in English | LILACS | ID: lil-685486


Acute infection with Trypanosoma cruzi results in intense myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The evolution toward this chronic cardiac form occurs in approximately 30% of all cases of T. cruzi infection. Suppression of delayed type hypersensitivity (DTH) has been proposed as a potential explanation of the indeterminate form. We investigated the effect of cyclophosphamide (CYCL) treatment on the regulatory mechanism of DTH and the participation of heart interstitial dendritic cells (IDCs) in this process using BALB/c mice chronically infected with T. cruzi. One group was treated with CYCL (20 mg/kg body weight) for one month. A DTH skin test was performed by intradermal injection of T. cruzi antigen (3 mg/mL) in the hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin test revealed increased thickness in antigen-injected footpads, which was more evident in the mice treated with CYCL than in those mice that did not receive treatment. The thickened regions were characterised by perivascular infiltrates and areas of necrosis. Intense lesions of the myocardium were present in three/16 cases and included large areas of necrosis. Morphometric evaluation of lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled with specific antibodies (CD11b and CD11c) and T. cruzi antigens were detected using a specific anti-T. cruzi antibody. Identification of T. cruzi antigens, sequestered in these cells using specific anti-T. cruzi antibodies was done, showing a significant increase in the number of these cells in treated mice. These results indicate that IDCs participate in the regulatory mechanisms of DTH response to T. cruzi infection.

Animals , Chagas Cardiomyopathy/drug therapy , Cyclophosphamide/pharmacology , Dendritic Cells/immunology , Hypersensitivity, Delayed/drug therapy , Immunosuppressive Agents/pharmacology , Trypanosoma cruzi , Antigen Presentation/immunology , Antigens, Protozoan/immunology , Chronic Disease , Chagas Cardiomyopathy/immunology , Hypersensitivity, Delayed/immunology , Mice, Inbred BALB C , Parasitemia/drug therapy , Parasitemia/immunology , Skin Tests
Botucatu; s.n; 2013. 76 p. ilus.
Thesis in Portuguese | LILACS | ID: lil-756020


O câncer colorretal (CCR) um dos principais tipos de tumor em todo mundo. Em alguns casos observa-se forte influência hereditária em seu desenvolvimento nas formas familiares, enquanto que na maioria dos pacientes (85%) essa doença se apresenta na forma esporádica, cuja origem é multifatorial, com grande influência da alimentação, tabagismo e etilismo, além de processos inflamatórios crônicos. Seu tratamento convencional consiste em intervenção cirúrgica acompanhada de terapias com doses elevadas de drogas citotóxicas. Apesar dessa intervenção radical, recidivas em pacientes com CCR são muito freqüentes, apontando para a necessidade de abordagens mais efetivas e para a possibilidade de combinação de diferentes formas de tratamento. Dada a importância do CCR como problema de saúde pública e da possibilidade de modulação do sistema imunológico dos pacientes, o presente trabalho é apresentado em dois capítulos, sendo o primeiro uma revisão de literatura sobre a doença propriamente dita, abordando os tratamentos empregados, a influência da resposta inflamatória em sua gênese e o papel da resposta imunológica na doença. Essa revisão foi redigida de acordo com as normas da revista Cancer Science. O segundo capítulo, redigido seguindo as normas da revista Cancer Immunology, Immunotherapy, refere-se ao desenvolvimento do estudo experimental, no qual foi avaliada a eficiência funcional de células dendríticas (DCs) humanas transfectadas com RNA total de células tumorais pré-tratadas com concentrações não tóxicas ou efetiva mínima de 5-fluorouracil (5-FU). Os resultados obtidos indicam que a transfecção das DCs com RNA de células tumorais expostas à droga aumenta sua capacidade de apresentação de antígenos alogênicos aos linfócitos T e de indução de resposta tumor-específica (geração in vitro de linfócitos T citotóxicos e produção de INF-γ)...

Colorectal cancer (CRC) is one of the most frequent tumor types worldwide, mainly in developed countries, and can be classified as inheritedfamilial (25%) or sporadic (75%) forms, which suggest an important relationship of gene-gene and gene-environment interactions in the development of the disease. CRC is characterized by genetic and epigenetic alterations, and is histologically featured by the infiltration of inflammatory cells among malignant and stromal cells. The most common inflammatory cells in tumor tissue are neutrophils, mast cells, natural killer cells, macrophages and dendritic cells as well as lymphocytes. However, the presence of these cells in CRC can both be associated with cancer inhibition and tumor progression, since the development a chronic inflammatory response can be a predisposal condition for the development of this type of cancer. Considering these multifactorial aspects of CRC development, in this review we present data on the main genetic and epigenetic aspects, and the influence of diet and inflammation on tumor progression...

Humans , Dendritic Cells/immunology , Colorectal Neoplasms/immunology
Biol. Res ; 46(4): 431-440, 2013. ilus, graf, tab
Article in English | LILACS | ID: lil-700405


Here we summarize 10 years of effort in the development of a biomedical innovation with global projections. This innovation consists of a novel method for the production of therapeutic dendritic-like cells called Tumor Antigen Presenting Cells (TAPCells®). TAPCells-based immunotherapy was tested in more than 120 stage III and IV melanoma patients and 20 castration-resistant prostate cancer patients in a series of phase I and I/II clinical trials. TAPCells vaccines induced T cell-mediated memory immune responses that correlated with increased survival in melanoma patients and prolonged prostate-specific antigen doubling time in prostate cancer patients. Importantly, more than 60% of tested patients showed a Delayed Type Hypersensitivity (DTH) reaction against the lysates, indicating the development of anti-tumor immunological memory that correlates with clinical benefits. The in vitro analysis of the lysate mix showed that it contains damage-associated molecular patterns such as HMBG-1 protein which are capable to improve, through Toll-like receptor-4, maturation and antigen cross-presentation of the dendritic cells (DC). In fact, a Toll-like receptor-4 polymorphism correlates with patient clinical outcomes. Moreover, Concholepas concholepas hemocyanin (CCH) used as adjuvant proved to be safe and capable of enhancing the immunological response. Furthermore, we observed that DC vaccination resulted in a three-fold increase of T helper-1 lymphocytes releasing IFN-γ and a two-fold increase of T helper-17 lymphocytes capable of producing IL-17 in DTH+ with respect to DTH- patients. Important steps have been accomplished for TAPCells technology transfer, including patenting, packaging and technology assessment. Altogether, our results indicate that TAPCells vaccines constitute an exceptional Chilean national innovation of international value.

Female , Humans , Male , Antigens, Neoplasm/immunology , Cancer Vaccines/administration & dosage , Dendritic Cells/immunology , Melanoma/therapy , Prostatic Neoplasms/therapy , Skin Neoplasms/therapy , Chile , Cell Extracts/immunology , Cell Extracts/therapeutic use , Melanoma/immunology , Neoplasm Staging , Prostatic Neoplasms/immunology , Skin Neoplasms/immunology , Treatment Outcome , /immunology