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J. pediatr. (Rio J.) ; 94(5): 546-553, Sept.-Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-975984


Abstract Objective: There is evidence of an important role of immune system changes in the triggering and maintenance of idiopathic nephrotic syndrome (INS). The aim of this study was to investigate the expression of cytokines in lymphocyte populations of patients with INS in comparison to healthy individuals, according to proteinuria. Methods: This cross-sectional study included 44 patients with INS and eight healthy children, matched for age and sex (controls). Patients were subdivided according to proteinuria: persistent proteinuria or partial remission (PP ≥ 300 mg/24 h, n = 17) and low proteinuria or complete remission (LP < 300 mg/24 h, n = 27). Ex vivo analysis of peripheral blood leukocytes by flow cytometry was performed using surface markers for T-lymphocytes, TCD4, TCD8, natural killer (NK) cells, NKT, and B-lymphocytes. Frequencies of intracellular cytokines were analyzed in these cells. Results: The frequencies of B-lymphocytes, NK cells, and NKT cells were lower in INS than in controls, whereas INS patients had a higher frequency of CD4+tumor necrosis factor (TNF)-α+ cells than controls. Cytotoxic-T-lymphocytes expressing IFN-γ were lower in INS than in controls. Patients with PP showed higher frequencies of CD4-T-lymphocytes expressing IFN-γ and TNF-α than controls. CD8-lymphocytes expressing TNF-α were increased in PP group when compared with LP and controls, while CD8+interferon (IFN)-γ+ cells were lower than in LP and in controls. Conclusion: Regardless the level of proteinuria, INS patients had increased expression of TNF-α in CD4-lymphocytes and reduced expression of IFN-γ in CD8-lymphocytes. Persistence of proteinuria was associated with higher levels of inflammatory markers.

Resumo Objetivo Há comprovação do importante papel das alterações no sistema imunológico no desencadeamento e manutenção da síndrome nefrótica idiopática (SNI). O objetivo deste estudo foi investigar a expressão das citocinas em populações de linfócitos de pacientes com SNI em comparação a indivíduos saudáveis e de acordo com a proteinúria. Métodos Este estudo transversal incluiu 44 pacientes com SNI e oito crianças saudáveis, pareados por idade e sexo (controles). Os pacientes foram subdivididos de acordo com a proteinúria: proteinúria persistente ou remissão parcial (PP ≥ 300 mg/24 h, n = 17) e proteinúria baixa ou remissão completa (PB < 300 mg/24 h, n = 27). A análise ex vivo de leucócitos no sangue periférico por citometria de fluxo foi feita utilizando marcadores de superfície para linfócitos T, TCD4, TCD8, células natural killer (NK), linfócitos NKT e B. As frequências das citocinas intracelulares foram analisadas nessas células. Resultados A frequência dos linfócitos B, células NK e células NKT foi menor em pacientes com SNI do que nos controles, ao passo que os pacientes com SNI apresentaram maior frequência de células CD4+fator de necrose tumoral (TNF)-α+ do que nos controles. Os linfócitos T citotóxicos que expressam interferon (IFN)-γ foram menores nos pacientes com SNI do que nos controles. Os pacientes com PP mostraram maiores frequências de linfócitos T CD4 que expressam IFN-γ e TNF-α que os controles. Os linfócitos CD8 que expressam TNF-α apresentaram aumento no grupo com PP, em comparação aos com PB e os controles, apesar de as células CD8+IFN-γ+ serem mais baixas nos pacientes com PB e nos controles. Conclusão Com relação ao nível de proteinúria, os pacientes com SNI apresentaram aumento na expressão de TNF-α nos linfócitos CD4 e expressão reduzida de IFN-γ nos linfócitos CD8. A persistência da proteinúria foi associada a maiores níveis de marcadores inflamatórios.

Humans , Male , Female , Child , Adolescent , Proteinuria/etiology , Killer Cells, Natural/immunology , T-Lymphocytes/immunology , Cytokines/immunology , Nephrotic Syndrome/immunology , Proteinuria/immunology , Proteinuria/blood , Biomarkers , Case-Control Studies , Cross-Sectional Studies , Cytokines/blood , Disease Progression , Flow Cytometry , Leukocyte Count , Nephrotic Syndrome/complications , Nephrotic Syndrome/blood
Rev. chil. endocrinol. diabetes ; 11(2): 62-68, abr. 2018. graf
Article in Spanish | LILACS | ID: biblio-914895


Aim: Analyze mi-146a and miR-155 expression and its correlation with the apoptosis of lymphocytes T in T1D and control patient. Patients and Methodology: 17 T1D patients (5 children between 8-14 yr and 12 adults between 19-29 yr). Activated and not activated peripheral mononuclear cells were studied were studied. Cellular activation with anti-CD3 and primary culture with interleukyne-2 by 5 days. Apoptosis assays through flow cytometry. miRNA through Taqman probes. Statistical analysis through Kruskal-Wallis and post-hoc Dunn's test. Results: Composition of virgin and memory T CD4 cells showed significant differences for stimulus response in control group (p = 0,0004). Increased memory cells count in control group activated by 7 days than basal (p = 0,0047). For early apoptosis differences were observed in days 3 and 7 with and without activation (p = 0,001). AICD apoptosis showed increases in control group after re-stimulation through TCR (p= 0,03). miR-146a expression was lower in recent-onset T1D children vs recent-onset DM1 adults (p = 0,0167). Conclusion: This study shows a differential miR-146a expression in T1D children with respect to T1D adult patients, diminished AICD mechanism in T1D and altered CD4+CD45RA-CD45R0+ memory cells generation in T1D adult patients.

Humans , Male , Female , Child , Adolescent , Adult , T-Lymphocytes/immunology , Apoptosis/immunology , Diabetes Mellitus, Type 1/immunology , MicroRNAs/genetics , MicroRNAs/immunology , Diabetes Mellitus, Type 1/genetics , Immunologic Memory
An. bras. dermatol ; 93(2): 242-250, Mar.-Apr. 2018. tab, graf
Article in English | LILACS | ID: biblio-887186


Abstract: Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation.

Humans , Skin/immunology , T-Lymphocytes/immunology , Dermatitis, Allergic Contact/immunology , Immunity, Innate/immunology , Cytokines/immunology , T-Lymphocytes, Regulatory/immunology , Toll-Like Receptors/immunology
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
Einstein (Säo Paulo) ; 16(4): eAO4278, 2018. tab, graf
Article in English | LILACS | ID: biblio-975101


ABSTRACT Objective: To investigate the correlation between total lymphocyte and CD3+ T cell counts in peripheral blood in renal transplant patients treated with anti-thymocyte globulin, and discuss related outcomes. Methods: A single-center, retrospective study involving 226 patients submitted to kidney transplant between 2008 and 2013, and treated with anti-thymocyte globulin for induction or treatment of cellular rejection. Doses were adjusted according to CD3+ T cell or total lymphocyte counts in peripheral blood. Results: A total of 664 paired samples were analyzed. The Spearman's correlation coefficient was 0.416 (p<0.001) for all samples combined; the overall Kappa coefficient was 0.267 (p<0.001). Diagnostic parameters estimated based on total lymphocyte counts were also calculated using the number of CD3+ T cells (gold standard), with a cut off of >20 cells/mm3. Conclusion: Total lymphocyte and CD3+ T cell counts in peripheral blood are not equivalent monitoring strategies in anti-thymocyte globulin therapy.

RESUMO Objetivo: Investigar a correlação entre a contagem de linfócitos totais e células T CD3+ no sangue periférico em receptores de transplante renal submetidos a tratamento com globulina antitimocitária, e discutir resultados relacionados. Métodos: Estudo retrospectivo de centro único envolvendo 226 pacientes submetidos a transplante renal entre 2008 e 2013 e tratados com globulina antitimocitária, para fins de indução ou tratamento de rejeição celular. As doses foram ajustadas de acordo com a contagem de células T CD3+ ou linfócitos totais no sangue periférico. Resultados: No total, 664 amostras pareadas foram analisadas. O coeficiente de correlação de Spearman para as amostras em geral foi de 0,416 (p<0,001) e o coeficiente Kappa, de 0,267 (p<0,001). Os parâmetros diagnósticos estimados com base na contagem de linfócitos totais foram recalculados, empregando-se o número de células T CD3+ (padrão-ouro) e adotando-se o ponto de corte >20 células/mm3. Conclusão: A contagem de linfócitos totais no sangue periférico não substitui a contagem de células T CD3+ enquanto estratégia de monitorização da terapia à base de globulina antitimocitária.

Humans , Male , Female , Adult , Kidney Transplantation , CD3 Complex , Thymocytes/immunology , Transplant Recipients , Graft Rejection/therapy , Isoantibodies/therapeutic use , Antibodies, Monoclonal/therapeutic use , T-Lymphocytes/immunology , Monitoring, Immunologic/instrumentation , Survival Analysis , Retrospective Studies , Lymphocyte Count , Flow Cytometry/methods , Immunotherapy/methods , Middle Aged
J. bras. nefrol ; 39(2): 181-185, Apr.-June 2017. graf
Article in English | LILACS | ID: biblio-893754


Abstract Introduction: Immunosuppression of T lymphocytes is required for preventing acute rejection after transplantation and for the treatment of chronic autoimmune and inflammatory diseases. The laboratory monitoring for this therapy is the measurement of T cells by immunophenotyping, aiming the target value of less than 20 cells per µL. Objective: To establish a cut-off point for the total number of lymphocytes in the automated blood cell count that reflects less than twenty T cells µL by immunophenotyping. Methods: We studied and evaluated 242 kidney transplant patients that had results of automated blood cell count and quantification of T cells by immunophenotyping technique. The patients were divided into two groups, depending on the T lymphocyte immunophenotyping rates established by lower and higher than 20 cells per µL. After, we evaluated the cut-off point for lymphocytes in the blood cell count with a specificity of 100% to exclude patients with high levels of T lymphocytes. Results: We found that the cut-off point of 70 lymphocytes per µL obtained by automated blood cell count showed 100% of specificity to exclude patients with T-cell counts higher than 20 cells per µL by immunophenotyping. Conclusion: The results found in this study may be helpful to monitor the immunosuppressive therapy in kidney transplant patients in places where a flow cytometer is not available, or when this equipment is not present in the full routine.

Resumo Introdução: A imunossupressão de linfócitos T é necessária para a prevenção da rejeição aguda em transplantes e no tratamento de doenças autoimunes e inflamatórias crônicas. O seu monitoramento laboratorial consiste na quantificação dos linfócitos T realizada pela técnica de imunofenotipagem, na qual o valor preconizado é manter inferior a 20 células/µL. Objetivo: Estabelecer um ponto de corte para o número de linfócitos totais no hemograma automatizado que reflita uma contagem de linfócitos T inferior a 20 células/µL por imunofenotipagem. Métodos: Foram avaliados 242 pacientes transplantados renais que continham resultados do hemograma automatizado e quantificação de linfócitos T por imunofenotipagem. Os pacientes foram divididos em dois grupos, conforme os valores de linfócitos T estabelecidos pela imunofenotipagem: inferiores e superiores a 20 células/µL. A partir disto, foi avaliado o ponto de corte de linfócitos no hemograma com especificidade de 100% para excluir os pacientes com valores elevados de linfócitos T. Resultados: Este estudo evidenciou que o ponto de corte de 70 linfócitos/µL obtidos pelo hemograma automatizado apresentou especificidade de 100% para excluir os pacientes com contagens de linfócitos T superiores a 20 células/µL na imunofenotipagem. Conclusão: Esta pesquisa poderá auxiliar no monitoramento da terapia imunossupressora em pacientes transplantados renais em locais que não possuem um citômetro de fluxo disponível, ou ainda quando este equipamento não se faz presente na rotina integral.

Humans , Male , Female , Middle Aged , T-Lymphocytes/immunology , Immunosuppression , Kidney Transplantation , CD3 Complex , Immunosuppressive Agents/therapeutic use , Antilymphocyte Serum/therapeutic use , Retrospective Studies , Immunophenotyping/methods , Drug Monitoring , Lymphocyte Count
Ann. hepatol ; 16(1): 94-106, Jan.-Feb. 2017. graf
Article in English | LILACS | ID: biblio-838091


Abstract: The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow- up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. identification: NCT01321112.

Humans , Male , Middle Aged , Aged , Liver Transplantation , Tacrolimus/administration & dosage , Cyclosporine/administration & dosage , Calcineurin Inhibitors/administration & dosage , Graft Rejection/prevention & control , Graft Survival/drug effects , Immunosuppressive Agents/administration & dosage , Mycophenolic Acid/administration & dosage , Time Factors , Transcription Factors/immunology , Drug Administration Schedule , T-Lymphocytes/immunology , Chi-Square Distribution , Odds Ratio , Multivariate Analysis , Prospective Studies , Risk Factors , Liver Transplantation/adverse effects , Treatment Outcome , Tacrolimus/adverse effects , Drug Monitoring/methods , Cyclosporine/adverse effects , Drug Therapy, Combination , Calcineurin Inhibitors , Graft Rejection/immunology , Immunosuppressive Agents/adverse effects , Kidney/drug effects , Kidney/physiopathology , Mycophenolic Acid/adverse effects
Rev. bras. anestesiol ; 66(2): 133-139, Mar.-Apr. 2016. tab, graf
Article in English | LILACS | ID: lil-777398


ABSTRACT BACKGROUND: Among the many changes caused by a surgical insult one of the least studied is postoperative immunosuppression. This phenomenon is an important cause of infectious complications of surgery such as surgical site infection or hospital acquired pneumonia. One of the mechanisms leading to postoperative immunosuppression is the apoptosis of immunological cells. Anesthesia during surgery is intended to minimize harmful changes and maintain perioperative homeostasis. The aim of the study was evaluation of the effect of the anesthetic technique used for total knee replacement on postoperative peripheral blood lymphocyte apoptosis. METHODS: 34 patients undergoing primary total knee replacement were randomly assigned to two regional anesthetic protocols: spinal anesthesia and combined spinal-epidural anesthesia. 11 patients undergoing total knee replacement under general anesthesia served as control group. Before surgery, immediately after surgery, during first postoperative day and seven days after the surgery venous blood samples were taken and the immunological status of the patient was assessed with the use of flow cytometry, along with lymphocyte apoptosis using fluorescent microscopy. RESULTS: Peripheral blood lymphocyte apoptosis was seen immediately in the postoperative period and was accompanied by a decrease of the number of T cells and B cells. There were no significant differences in the number of apoptotic lymphocytes according to the anesthetic protocol. Changes in the number of T CD3/8 cells and the number of apoptotic lymphocytes were seen on the seventh day after surgery. CONCLUSION: Peripheral blood lymphocyte apoptosis is an early event in the postoperative period that lasts up to seven days and is not affected by the choice of the anesthetic technique.

RESUMO JUSTIFICATIVA E OBJETIVO: Dentre as muitas alterações causadas por uma ferida cirúrgica, uma das menos estudadas é a imunossupressão pós-operatória. Esse fenômeno é uma causa importante das complicações infecciosas relacionadas à cirurgia, como infecção do sítio cirúrgico ou pneumonia nosocomial. Um dos mecanismos que levam à imunossupressão pós-operatória é a apoptose de células imunológicas. Durante a cirurgia, a anestesia se destina a minimizar as alterações prejudiciais e manter a homeostase perioperatória. O objetivo deste estudo foi avaliar o efeito da técnica anestésica usada para artroplastia total de joelho sobre a apoptose em linfócitos de sangue periférico no pós-operatório. MÉTODOS: Trinta e quatro pacientes submetidos à artroplastia total primária de joelho foram randomicamente designados para dois protocolos de anestesia regional: raquianestesia e bloqueio combinado raqui-peridural. Onze pacientes submetidos à artroplastia total do joelho sob anestesia geral formaram o grupo controle. Antes da cirurgia, logo após a cirurgia, durante o primeiro dia de pós-operatório e sete dias após a cirurgia, amostras de sangue venoso foram colhidas e o estado imunológico do paciente foi avaliado com o uso deflow cysts 87 m, juntamente com apoptose de linfócitos com o uso de microscopia de fluorescência. RESULTADOS: Apoptose em linfócitos de sangue periférico foi observada imediatamente no pós-operatório e acompanhada por uma redução do número de células T e B. Não houve diferença significativa no número de linfócitos apoptóticos de acordo com o protocolo anestésico. Alterações no número de células T CD3/8 e no número de linfócitos apoptóticos foram observadas no sétimo dia após a cirurgia. CONCLUSÃO: Apoptose em linfócitos de sangue periférico é um evento precoce no período pós-operatório que dura até sete dias e não é afetado pela escolha da técnica anestésica.

Humans , Male , Female , Aged , Aged, 80 and over , Apoptosis/immunology , Arthroplasty, Replacement, Knee/methods , Anesthesia, Epidural/methods , Anesthesia, Spinal/methods , Postoperative Complications/immunology , Postoperative Complications/epidemiology , B-Lymphocytes/immunology , T-Lymphocytes/immunology , Arthroplasty, Replacement, Knee/adverse effects , Flow Cytometry , Immune Tolerance , Anesthesia, General/methods , Microscopy, Fluorescence , Middle Aged
Braz. j. med. biol. res ; 49(4): e5062, 2016. tab, graf
Article in English | LILACS | ID: biblio-951667


Type 2 diabetes mellitus (T2D) is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old) with T2D and 20 nonsmoking men (49.4±7.6 years old) who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL)-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05). The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01). In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease.

Humans , Male , Adult , Middle Aged , Cytokines/blood , T-Lymphocyte Subsets/metabolism , Diabetes Mellitus, Type 2/blood , Reference Values , C-Reactive Protein/metabolism , T-Lymphocytes/cytology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Case-Control Studies , T-Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/immunology , Statistics, Nonparametric , Lymphocyte Count , Diabetes Mellitus, Type 2/immunology , Flow Cytometry , Immunity, Cellular
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
Arch. endocrinol. metab. (Online) ; 59(3): 202-209, 06/2015. tab, graf
Article in English | LILACS | ID: lil-751312


Objective Acarbose and trans-chalcone are glucosidase inhibitors whose beneficial effects have been demonstrated in diabetes. The present study aimed at investigating their potential effects in obesity.Materials and methods NMRI male mice (n = 48) were subjected to a high fat diet for four weeks, which induced an initial state of obesity. One control group was given normal rodent diet. Obese animals were then switched to normal rodent diet, and divided to four groups (n = 12 in each): untreated, sham (receiving grape seed oil), and experimental groups receiving acarbose and trans-chalcone (12 mg/kg) during eight weeks. Body weight, blood glucose and other biochemical parameters including triglycerides (TG), cholesterol, HDL, AST, and ALT were measured, as well as leptin, adiponectin, TNF-α, and total antioxidant capacity (TAC). Histological studies were performed on adipose cells and liver tissue samples.Results All factors were affected in a positive manner by acarbose, save for body weight, blood sugar and leptin levels, on which acarbose effects, although observable, were not statistically significant. Grape seed oil, used as a solvent for trans-chalcone was found to possess significant effect on TG and TAC, and had beneficial effects on other factors including liver enzymes and cholesterol. Trans-chalcone effects were significant on HDL, leptin and ALT. All compounds seemed to be able to affect fat deposition in liver tissue, and decrease the size of adipose tissue cells to some extent.Conclusion In conclusion, the tested compounds were able to affect lipid accumulation in tissues and influence adipokines, which may result in an enhanced state with regard to inflammation and oxidative stress. Arch Endocrinol Metab. 2015;59(3):202-9.

Animals , Humans , Mice , /metabolism , Carcinoma, Non-Small-Cell Lung/immunology , Cytokines/metabolism , Lung Neoplasms/immunology , Programmed Cell Death 1 Receptor/metabolism , ErbB Receptors/metabolism , T-Lymphocytes/immunology , Tumor Escape , /genetics , Cell Line , Carcinoma, Non-Small-Cell Lung/metabolism , Gene Expression Regulation, Neoplastic , Lymphocyte Activation , Lung Neoplasms/metabolism , Mice, Transgenic , Oncogenes , Programmed Cell Death 1 Receptor/genetics , ErbB Receptors/genetics , Signal Transduction , Tumor Microenvironment
Mem. Inst. Oswaldo Cruz ; 110(3): 414-421, 05/2015. tab, graf
Article in English | LILACS | ID: lil-745978


The aim of this review is to describe the contributions of the knowledge of T-cell responses to the understanding of the physiopathology and the responsiveness to etiological treatment during the chronic phase of Chagas disease. T-helper (Th)1 and interleukin (IL)-10 Trypanosoma cruzi-specific T-cells have been linked to the asymptomatic phase or to severe clinical forms of the disease, respectively or vice versa, depending on the T. cruzi antigen source, the patient’s location and the performed immunological assays. Parasite-specific T-cell responses are modulated after benznidazole (BZ) treatment in chronically T. cruzi-infected subjects in association with a significant decrease in T. cruzi-specific antibodies. Accumulating evidence has indicated that treatment efficacy during experimental infection with T. cruzi results from the combined action of BZ and the activation of appropriate immune responses in the host. However, strong support of this interaction in T. cruzi-infected humans remains lacking. Overall, the quality of T-cell responses might be a key factor in not only disease evolution, but also chemotherapy responsiveness. Immunological parameters are potential indicators of treatment response regardless of achievement of cure. Providing tools to monitor and provide early predictions of treatment success will allow the development of new therapeutic options.

Humans , Chagas Disease/immunology , Nitroimidazoles/therapeutic use , T-Lymphocytes/immunology , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi/immunology , Antigens, Protozoan/immunology , Chronic Disease , Chagas Disease/drug therapy , T-Lymphocytes/drug effects , Trypanosoma cruzi/drug effects
Cad. saúde pública ; 31(3): 463-475, 03/2015. tab, graf
Article in English | LILACS | ID: lil-744840


Cyberbullying is a new form of violence that is expressed through electronic media and has given rise to concern for parents, educators and researchers. In this paper, an association between cyberbullying and adolescent mental health will be assessed through a systematic review of two databases: PubMed and Virtual Health Library (BVS). The prevalence of cyberbullying ranged from 6.5% to 35.4%. Previous or current experiences of traditional bullying were associated with victims and perpetrators of cyberbullying. Daily use of three or more hours of Internet, web camera, text messages, posting personal information and harassing others online were associated with cyberbullying. Cybervictims and cyberbullies had more emotional and psychosomatic problems, social difficulties and did not feel safe and cared for in school. Cyberbullying was associated with moderate to severe depressive symptoms, substance use, ideation and suicide attempts. Health professionals should be aware of the violent nature of interactions occurring in the virtual environment and its harm to the mental health of adolescents.

Cyberbullying, uma nova forma de violência expressa por meio da mídia eletrônica, tem preocupado pais, educadores e pesquisadores. A associação entre cyberbullying e a saúde mental dos adolescentes será revisada. Revisão sistemática em duas bases de dados: PubMed e a Biblioteca Virtual em Saúde (BVS). A prevalência do cyberbullying variou entre 6,5% a 35,4%. Bullying tradicional prévio ou atual estava associado às vítimas e agressores do cyberbullying. Uso diário de três ou mais horas de Internet, web câmera, mensagens de texto, postar informações pessoais e assediar outros online estavam associados ao cyberbullying. "Cybervítimas" e cyberbullies tinham mais problemas emocionais, psicossomáticos, dificuldades sociais, e não se sentiam seguros e cuidados na escola. O cyberbullying estava associado à sintomatologia depressiva moderada e grave, uso de substâncias, ideação e tentativas de suicídio. Profissionais de saúde devem conhecer as interações de natureza violenta que ocorrem no ambiente virtual e de seus agravos para a saúde mental dos adolescentes.

Se revisa la asociación entre el acoso cibernético y la salud mental de los adolescentes. Se realiza una revisión sistemática de dos bases de datos: PubMed y la Biblioteca Virtual en Salud (BVS). La prevalencia de ciberacoso varió de un 6,5% a un 35,4%. Los acosos cibernéticos tradicionales -pasados o actuales- se asociaron con las víctimas y los acosadores cibernéticos. El uso diario de tres o más horas de Internet, cámara web, mensajes de texto, la publicación de información personal y acosar a los demás se asociaron con el acoso cibernético. Cibervíctimas y acosadores cibernéticos tenían más problemas emocionales, psicosomáticos, dificultades sociales y no se sentían seguros y cuidados en la escuela. El ciberacoso se asoció con síntomas de moderados a graves de depresión, abuso de sustancias, ideación suicida e intentos de suicidio. Los profesionales de salud deben conocer la naturaleza violenta de las interacciones que se producen en el entorno virtual y sus peligros para la salud mental de los adolescentes.

Animals , Mice , Antibody Formation/immunology , Poly(ADP-ribose) Polymerases/deficiency , B-Lymphocytes/immunology , Cell Proliferation , Cells, Cultured , Germinal Center/immunology , Immunization , Immunoglobulin Class Switching/immunology , Immunoglobulins/blood , Lipopolysaccharides/immunology , Lymphocyte Activation/immunology , Lymphocyte Cooperation/immunology , Mice, Mutant Strains , Poly(ADP-ribose) Polymerases/metabolism , T-Lymphocytes/immunology
Article in English | IMSEAR | ID: sea-158451


Background & objectives: Since the 2006 massive outbreaks, chikungunya (CHIK) is a major public health concern in India. The aim of this study was to assess envelope specific immune responses in patients with chikungunya infection. Methods: This study included 46 hospitalized patients with chikungunya virus infection (encephalitis, n=22, other systemic involvement, OSI, n=12, classical, n=12) and six controls from Ahmedabad city, Gujarat, India. T cell responses and the levels of Th1, pro/ anti-inflammatory cytokines against the CHIK virus envelope antigens were assessed by lymphocyte proliferation assay and by cytometric bead array in flow cytometry, respectively. Results: Lymphoproliferative response was uniform among the patients. Comparisons of cytokines revealed significantly higher levels of interleukin (IL)-4 and IL-5 in encephalitis, OSI and classical patients versus controls. The levels of tumour necrosis factor (TNF)-α were higher in classical patients categories compared to the controls. Interferon (IFN)-γ levels were lower in encephalitis patients versus control. Interpretation & conclusions: Our findings showed recognition of T cell epitopes on the envelope region of chikungunya virus by all patient categories. Lower level of IFN-γ may be associated with the severity of disease in these patients.

Chikungunya Fever/diagnosis , Chikungunya Fever/epidemiology , Chikungunya Fever/immunology , Cytokines/analysis , Humans , India , T-Lymphocytes/immunology , T-Lymphocyte Subsets/immunology
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
Article in English | WPRIM | ID: wpr-61564


Epstein Barr virus (EBV)-associated lymphoproliferative diseases (LPDs) express all EBV latent antigens (type III latency) in immunodeficient patients and limited antigens (type I and II latencies) in immunocompetent patients. Post-transplantation lymphoproliferative disease (PTLD) is the prototype exhibiting type III EBV latency. Although EBV antigens are highly immunogenic, PTLD cell proliferation remains unchecked because of the underlying immunosuppression. The restoration of anti-EBV immunity by EBV-specific T cells of either autologous or allogeneic origin has been shown to be safe and effective in PTLDs. Cellular therapy can be improved by establishing a bank of human leukocyte antigen-characterized allogeneic EBV-specific T cells. In EBV+ LPDs exhibiting type I and II latencies, the use of EBV-specific T cells is more limited, although the safety and efficacy of this therapy have also been demonstrated. The therapeutic role of EBV-specific T cells in EBV+ LPDs needs to be critically reappraised with the advent of monoclonal antibodies and other targeted therapy. Another strategy involves the use of epigenetic approaches to induce EBV to undergo lytic proliferation when expression of the viral thymidine kinase renders host tumor cells susceptible to the cytotoxic effects of ganciclovir. Finally, the prophylactic use of antiviral drugs to prevent EBV reactivation may decrease the occurrence of EBV+ LPDs.

Antiviral Agents/therapeutic use , Cell- and Tissue-Based Therapy , DNA Methylation , Epstein-Barr Virus Infections/complications , Genome, Viral , Hematopoietic Stem Cell Transplantation , Herpesvirus 4, Human/physiology , Humans , Immunotherapy, Adoptive , Lymphoproliferative Disorders/diagnosis , Organ Transplantation/adverse effects , T-Lymphocytes/immunology , Transplantation, Homologous , Virus Latency
Article in English | WPRIM | ID: wpr-61562


Epstein-Barr virus, a ubiquitous human herpesvirus, can induce both lytic and latent infections that result in a variety of human diseases, including lymphoproliferative disorders. The oncogenic potential of Epstein-Barr virus is related to its ability to infect and transform B lymphocytes into continuously proliferating lymphoblastoid cells. However, Epstein-Barr virus has also been implicated in the development of T/natural killer cell lymphoproliferative diseases. Epstein-Barr virus encodes a series of products that mimic several growth, transcription and anti-apoptotic factors, thus usurping control of pathways that regulate diverse homeostatic cellular functions and the microenvironment. However, the exact mechanism by which Epstein-Barr virus promotes oncogenesis and inflammatory lesion development remains unclear. Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases often have overlapping clinical symptoms as well as histologic and immunophenotypic features because both lymphoid cell types derive from a common precursor. Accurate classification of Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases is a prerequisite for appropriate clinical management. Currently, the treatment of most T/natural killer cell lymphoproliferative diseases is less than satisfactory. Novel and targeted therapies are strongly required to satisfy clinical demands. This review describes our current knowledge of the genetics, oncogenesis, biology, diagnosis and treatment of Epstein-Barr virus-associated T/natural killer cell lymphoproliferative diseases.

Cell Transformation, Viral , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human/physiology , Humans , Killer Cells, Natural/immunology , Lymphoproliferative Disorders/diagnosis , T-Lymphocytes/immunology
Article in English | WPRIM | ID: wpr-142451


Atherosclerosis is a chronic progressive inflammatory disorder and the leading cause of cardiovascular mortality. Here we assessed the dynamic changes of T-cell-derived cytokines, such as inteferon (IFN)-gamma, interleukin (IL)-17 and IL-4, during the progression of atherosclerosis in apolipoprotein E-null (ApoE(-/-)) mice, to understand the role of immune responses in different stages of atherosclerosis. Male ApoE(-/-) mice were fed a high-fat, western-type diet (WD: 21% lipid, 1.5% cholesterol) after 5 weeks of age and were compared with C57BL/6 wild-type control mice fed a standard chow diet. Atherosclerotic lesions appeared in the aortic sinus of ApoE(-/-) mice 4 weeks after WD and the lesions progressed and occupied >50% of the total sinus area 16 weeks after WD. Aortic IL-17 mRNA and protein expression started to increase in ApoE(-/-) mice after 4 weeks on the WD and peaked at around 8-12 weeks on the WD. In terms of systemic expression of T-cell-derived cytokines, IL-17 production from splenocytes after anti-CD3/CD28 stimuli increased from 4 weeks on the WD, peaked at 12 weeks and returned to control levels at 16 weeks. The production of IFN-gamma and IL-4 (Th1 and Th2 cytokines, respectively) from splenocytes was delayed compared with IL-17. Taken together, the present data indicate that Th17 cell response may be involved at an early stage in the development of atherosclerosis.

Animals , Aorta/metabolism , Apolipoproteins E/genetics , Atherosclerosis/etiology , Diet, High-Fat/adverse effects , Gene Deletion , Interferon-gamma/genetics , Interleukin-17/genetics , Male , Mice, Inbred C57BL , Mice, Knockout , T-Lymphocytes/immunology , Up-Regulation