Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection / 医学前沿

The ongoing pandemic of Coronavirus disease 19 (COVID-19) is caused by a newly discovered β Coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination. Here we examined, using ELISA, the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6-7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection. All samples were positive for IgGs against the S- and N-proteins of SARS-CoV-2. Notably, 14 samples available at 6-7 months post-infection all showed significant neutralizing activities in a pseudovirus assay, with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2. Furthermore, in 10 blood samples from cases at 6-7 months post-infection used for memory T-cell tests, we found that interferon γ-producing CD4

Evaluation of immunological parameters in pregnant women: low levels of B and NK cells / Avaliação dos parâmetros imunológicos em mulheres gestantes: baixos níveis de células B e NK

Abstract Objective To describe the immunological and hematological reference intervals of low-risk pregnant women. Methods A cross-sectional retrospective database analysis of a basic and translational study analyzing the hematological evaluation blood counts and immunophenotyping of TCD3 + , TCD4 + , TCD8 + , B, and natural killer (NK) cells of the peripheral blood in 79 low-risk pregnant women and of 30 control women from the state of Pernambuco, Brazil, was performed. Results No significant differences were detected between the hematological profiles of the 2nd and 3rd trimesters. Nevertheless, the median level of B cells decreased significantly in the 2nd (174 x 103 μL; p < 0.002) and 3rd trimesters (160 x 103 μL; p < 0.001), compared with the control group (296 x 103 μL). Similarly, the median level of NK cells was lower in the 2nd (134 x 103 μL; p < 0.0004) and 3rd trimesters (100 x 103 μL, p < 0.0004), compared with the control group (183 x 103 μL). In contrast, relative TCD4+ and TCD8+ levels increased in the 2nd and 3rd trimesters compared with the controls (TCD4 + : 2nd trimester = 59%; p < 0.001; 3rd trimester = 57%; p < 0.01; control = 50%; and TCD8 + : 2nd trimester = 31%; p < 0.001; 3rd trimester = 36%; p < 0.01; control = 24%). Conclusion Low-risk pregnant women have ~ 40% less B and NK cells in the peripheral blood, compared with non-pregnant women. These parameters may improve health assistance for mothers and contribute to define reference values for normal pregnancies.

Resumo Objetivo Descrever o intervalo de referência imunológico e hematológico de gestantes de baixo risco. Métodos Realizou-se uma análise retrospectiva, de um estudo básico e translacional, analisando o perfil hematológico e a imunofenotipagem das células TCD3 + , TCD4 + , TCD8 + , B e natural killer (NK) do sangue periférico de 79 gestantes de baixo risco e de 30 mulheres (controles) do estado de Pernambuco, Brasil. Resultados Não observamos diferenças significativas entre os perfis hematológicos do 2° e 3° trimestres. No entanto, houve redução das células B no 2° (média = 174 x 103 μL; p < 0,002) e no 3° trimestres (160 x 103 μL; p < 0,001), comparado como grupo controle (296 x 103 μL). A mediana das células NK foi menor no 2° (134 x 103 μL; p < 0,0004) e no 3° trimestres (100 x 103 μL; p < 0,0004), comparado com o grupo controle (183 x 103 μL). Porém, o percentual de TCD4+ e de TCD8+ aumentou no 2° e 3° trimestres em relação aos controles (TCD4 + : 2° trimestre = 59%; p < 0,001; 3° trimestre = 57%; p < 0,01; controle = 50%; e TCD8 + : 2° trimestre = 31%; p < 0,001; 3° trimestre = 36%; p < 0,01; controle = 24%). Conclusão Mulheres grávidas de baixo risco têm ~ 40% menos células B e NK no sangue periférico em comparação com mulheres não grávidas. Estes parâmetros podem melhorar a assistência à saúde das mães e contribuir para a definição de valores de referência para gestações normais.

Immunosenescence: participation of T lymphocytes and myeloid-derived suppressor cells in aging-related immune response changes / Imunosenescência: participação de linfócitos T e células mieloides supressoras nas alterações da resposta imune relacionadas ao envelhecimento

ABSTRACT Healthy aging is partly related to appropriate function of the immune system. As already reported, some changes in this system are observed, including reduced number and repertoire of T cells due to thymic involution, accumulation of memory T cells by chronic infections, homeostatic proliferation compensating for the number of naïve T cells, decreased proliferation of T cells against a stimulus, telomere shortening, replicative senescence of the T cells, and inflammaging, besides the accumulation of myeloid-derived suppressor cells. The purpose of this article is to clarify each of these changes, aiming to minimize limitations of immunosenescence. If such associations can be established, these cells may be used as early and less invasive markers of aging-related diseases, as well as to indicate interventions, evaluate the efficacy of interventions and be a tool to achieve longevity with quality of life.

RESUMO O envelhecimento saudável está relacionado, pelo menos em parte, com a função adequada do sistema imunológico. Isso porque já foi relatado que, com o envelhecimento, algumas mudanças desse sistema são observadas, como a diminuição da percentagem e do repertório de células T pela involução tímica, acúmulo de células T de memória por infecções crônicas, compensação do número de células T naïve por proliferação homeostática, diminuição da capacidade de proliferação das células T frente a um estímulo, encurtamento dos telômeros, senescência replicativa das células T, e inflammaging, além do acúmulo de células mieloides supressoras. Este artigo visa esclarecer cada uma das mudanças, mencionadas, com o intuito de buscar meios de minimizar as limitações da imunosenescência. Caso seja possível estabelecer tais relações, essas células podem ser utilizadas como marcadores precoces e pouco invasivos de doenças relacionadas ao envelhecimento, além da possibilidade de serem utilizadas para indicar intervenções, avaliar a eficácia das intervenções e como ferramenta para alcance da longevidade com qualidade de vida.

Immune System Dysfunction in the Elderly

ABSTRACT Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic low-level inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

Caracterización del infiltrado linfocitario (CD, CD4, CD8, CD45RO y FOXP3) e inestabilidad microsatelital en pacientes con cáncer colorrectal / Lymphocyte infiltration and microsatellite instability in colorectal cancer patients

Background: In colorectal cancer (CRC) patients, lymphocyte infiltration (LI) and microsatellite instability (MSI) have been associated with better prognosis. Aim: To analyze the association between components of LI (CD3/CD4/CD8/CD45R0/FoxP3) and MSI status with metastatic stages in CRC patients. Material and Methods: Prospective study of 109 patients diagnosed with CRC. The expression of CD3, CD4, CD8, CD45R0 and FoxP3 markers, was evaluated by immunohistochemical analysis, and tumors were classified into negative, low and intense expression. The MSI was assessed with seven markers amplified by PCR from normal and tumoral DNA. Tumors were grouped in MSS (stable)/MSI-low and MSI-high. Statistical analysis was performed with Fischer's exact test. Results: 29 percent, 28 percent, 12 percent and 86 percent of tumors exhibits intense expression of CD3+, CD4+, CD8+ and CD45RO+ lymphocytes, respectively. 84 percent of the tumors presented MSS/ MSI-low and 16 percent had MSI-high. Tumors that show a high density of T cells (CD3+, CD4+ y CD45R0+) are associated with early stage tumors (I and II) (p = 0.023; p = 0.030 and p = 0.003, respectively). Additionally, there was a significant association between the MSS/MSI-low tumors and a reduced ability to recruit CD8+ cytotoxic T lymphocytes (p = 0.037) and CD3+ (p = 0.064). Conclusion: There is an association between high densities of CD3+, CD4+ and CD45RO+ lymphocytes and non-metastatic tumors. In addition, MSS/ MSI-low tumors are associated with a lower recruitment of CD8+ and CD3+ lymphocytes.

Introducción: En el cáncer colorrectal (CCR), se sugiere que un mejor pronóstico podría asociarse a una respuesta inmune antitumoral (del huésped) y/o a la presencia de una alta inestabilidad microsatelital (MSI). Objetivo: Determinar si los niveles de expresión de los marcadores de linfocitos T (CD3/CD4/CD8/ CD45RO/FoxP3) y el estado de MSI se asocian a estadios metastásicos en pacientes con CCR. Material y Método: Estudio prospectivo de 109 pacientes con diagnóstico de CCR. El análisis de expresión de los marcadores CD3/CD4/CD8/CD45RO/FoxP3 fue realizado por inmunohistoquímica; los tumores fueron clasificados en negativo, débil e intenso. La MSI fue evaluada con siete marcadores amplificados desde ADN normal y tumoral; los tumores fueron agrupados en: MSS (estable)/MSI-baja y MSI-alta. El análisis estadístico fue realizado con el test exacto de Fischer. Resultados: Una intensa expresión de los marcadores CD3+, CD4+, CD8+ y CD45RO+, fue observada en el 29 por ciento, 28 por ciento, 12 por ciento y 86 por ciento de los tumores, respectivamente. El 16 por ciento de los tumores presentó MSI-alta. Los tumores que presentan una alta densidad de linfocitos T (CD3+, CD4+ y CD45RO+) se asocian a estadios tempranos I-II (p = 0,023; p = 0,030 y p = 0,003, respectivamente). Adicionalmente, se identificó una asociación estadística significativa entre los tumores con MSS/MSI-baja y una menor capacidad de reclutar linfocitos T citotóxicos CD8+ (p = 0,037) y totales CD3+ (p = 0,064). Conclusión: Existe una asociación entre altas densidades de linfocitos T CD3+, CD4+ y CD45RO+ y tumores con estadios no metastásicos. Además, tumores con MSS/MSI-baja se asocian a un menor reclutamiento de linfocitos T CD8+ y CD3+.

Aggressive Multilocular Osteoblastoma in the Mandible: A Rare and Difficult Case to Diagnose

Osteoblastoma is a benign neoplasia and is uncommon in the jaws. In some cases, this lesion presents extremely aggressive local characteristics and is termed aggressive osteoblastoma. Because the clinical, radiographic and histopathologic characteristics are similar to those of a variety of benign and malignant tumors, it poses a diagnostic dilemma. This report presents a case of an aggressive osteoblastoma in the mandible and discusses the differential diagnosis of this lesion. A 13-year-old white male sought the Stomatology Clinic at the State University of Paraíba, Campina Grande, PB, Brazil, complaining of asymptomatic swelling on the left side of his face. Cone-beam computerized tomography showed a multilocular, hypodense bone lesion, located in the body of the left mandible and lower third of the ascending ramus. The initial diagnostic hypothesis was juvenile ossifying fibroma or osteosarcoma. After histopathologic examination, the final diagnosis was aggressive osteoblastoma. Surgical resection with a safety margin was performed. There was no evidence of recurrence after a follow-up period of 4 years.

O osteoblastoma é uma neoplasia benigna e incomum nos maxilares. Em alguns casos esta lesão apresenta características locais extremamente agressivas, sendo denominada osteoblastoma agressivo. Devido às características clínicas, radiográficas e histopatológicas serem similares a uma variedade de tumores benignos e malignos, o seu diagnóstico é um dilema. Este relato apresenta o caso de um osteoblastoma agressivo na mandíbula e discute o diagnóstico diferencial desta lesão. Paciente, branco, 13 anos de idade, foi atendido na Clínica de Estomatologia da Universidade Estadual da Paraíba, Campina Grande, PB, Brasil, queixando-se de aumento de volume assintomático do lado esquerdo de sua face. A tomografia computadorizada de feixe cônico revelou uma lesão óssea hipodensa multilocular, localizada no corpo do lado esquerdo da mandíbula e no terço inferior do ramo ascendente da mandíbula. A hipótese diagnóstica foi de fibroma ossificante juvenil e osteosarcoma. Após exame histopatológico, o diagnóstico final foi osteoblastoma agressivo. Foi realizada ressecção cirúrgica com margem de segurança. Não houve sinais de recorrência após 4 anos de acompanhamento.

Visión panorámica del sistema inmune / Panoramic vision of the inmune system

El sistema inmune media numerosas patologías, por lo que es importante conocer su estructura y funcionamiento. Se clasifica en innato y adquirido. El sistema inmune innato brinda una temprana e inespecífica respuesta contra los microorganismos. El sistema inmune adquirido humoral y celular nos brinda una respuesta específica para diferentes moléculas, posee memoria frente a los antígenos y diversidad para reaccionar a una gran variedad de antígenos.

The immune system mediates numerous pathologies functions por functioning it is important to know its structure and functioning. The immune system is classified into innate and adaptive immunity. The innate immunity provides early and non-specific response against microbes. The adaptive humoral and cellular immunity gives specificy for distinct molecules and has memory to enhance response to antigen and diversity to responde to large variety of antigen

Inmunología del embarazo / Immunology of pregnancy

Uno de los fenómenos que abre más interrogantes en la Inmunología es ¿Por qué el embrión, comportándose como un injerto semialogénico, no es rechazado por la madre? Se sabe que la madre produce una activa respuesta inmunológica frente al feto y sin embargo, en condiciones normales, el rechazo inmunológico no se produce. En el presente trabajo de revisión, se describen algunos mecanismos por medio de los cuales se genera la tolerancia inmunológica específica de la madre hacia el embrión. Todos estos mecanismos son interdependientes, y en conjunto constituyen una trama para evitar el rechazo fetal. Aquí se detalla la acción de las hormonas sexuales femeninas sobre el sistema inmunológico, el cambio del perfil de citoquinas, la generación de proteínas inmunomoduladoras y de anticuerpos bloqueantes, el efecto de la expresión de los HLA-G y el papel de algunas células inmunocompetentes como los linfocitos T reguladores, las células dendríticas y las células asesinas naturales o Natural Killer. Asimismo se detallan otras vías por las cuales el embrión se defiende del ataque inmunológico materno como la inducción de la apoptosis en el endometrio y en los leucocitos, el metabolismo de hierro y triptofano, la inhibición del sistema del complemento y la expresión de anexinas.

One of the phenomena that offers more questions in Immunology is: Why the embryo, behaving like a semialogenic graft, is not rejected by the mother? It is known that the mother produces an active immunological response against the fetus and, nevertheless, in normal conditions, the immunological rejection does not take place. In the present work of revision, some mechanisms are described by means of which the specific immunological tolerance of the mother is generated towards the embryo. All these mechanisms are interdependent and altogether they constitute a safety network to avoid the fetal rejection. Here the effects of female sex hormones on the immunological system, the change of the profile of cytokines, the generation of immunomodulating proteins and blocking antibodies, the effect of the expression of the HLA-G and the paper of some cells, like Regulatory T lymphocytes, dendritic and Natural Killer cells, are detailed. Also other routes by which the embryo defends itself of the maternal immunological attack are described, like the induction of apoptosis in the endometrium and leukocytes, the tryptophan and iron metabolisms, the inhibition of the complement system and the expression of annexins.

El sistema inmunológico también envejece / The immune system ages too

El sistema inmunológico envejece con el paso del tiempo al igual que otras funciones del organismo. Contrariamente a lo que se creía, la respuesta inmune es una de las funciones corporales que más profundamente se ve afectada por el envejecimiento (Ruiz Fernández NA, Solano L, 2001). Esto nos obliga a tomar ciertos recaudos antes de proceder a efectuar alguna técnica invasiva en personas mayores, aún aparentemente sanas, ya que en algunos casos los riesgos son grandes. La mortalidad debida a infecciones es cinco veces mayor en los ancianos. En este artículo se describen cuáles son los cambios encontrados y cómo tratar de evitar sus consecuencias.

NFAT regulates CSF-1 gene transcription triggered by L-selectin crosslinking

L-selectin is a member of the selectin family that play an important role both in mediating the initial capture and subsequent rolling of leukocytes along the endothelial cells. Furthermore, L-selectin can function as a signal molecule. In our previous studies, we reported that L-selectin ligation could regulate CSF-1 (colony-stimulating factor-1) gene transcription, in which AP-1 acts as a crucial transcriptional factor. Here we investigated the function of the NFAT in the CSF-1 gene transcriptional events. We found that overexpression of WT NFAT induce CSF-1 gene transcription greatly in the activated Jurkat cells. Furthermore, we found that NFAT can be recruited to the nucleus after L-selectin ligation, and the nuclear NFAT interacts with the CSF-1 promoter region to regulate CSF-1 gene transcription in the L-s electin ligation activated Jurkat cells. These results indicate that nuclear NFAT can activate CSF-1 gene transcription by connecting with the CSF-1 promoter in the signaling events induced by L-selectin ligation.

Bone Marrow T Cells are Superior to Splenic T Cells to Induce Chimeric Conversion After Non-Myeloablative Bone Marrow Transplantation

BACKGROUND/AIMS: The bone marrow functions not only as the primary B-lymphocyte-producing organ but also as a secondary lymphoid organ for CD4 and CD8 cell responses and a site of preferential homing and persistence for memory T cells. Bone marrow T (BM-T) cells are distinguished from peripheral blood T cells by surface phenotype, cytokine secretion profile, and immune functions. In this study, we evaluated the alloreactive potential of donor lymphocyte infusion (DLI) using BM-T cells in mixed chimerism compared to that using spleen T (SP-T) cells. METHODS: Cells were prepared using established procedures. BM-T cells were obtained as a by-product of T-cell depletion in BM grafting and then cryopreserved for subsequent DLI. We performed DLI using BM-T cells in allogeneic mixed chimera mice on post-BMT day 21. RESULTS: When the same dose of T cells, 5-10x10(5) (Thy1.2+), fractionated from BM and spleen were administered into mixed chimeras, the BM-T group showed complete chimeric conversion, with self-limited graft-versus-host disease (GVHD) and no pathological changes. However, the SP-T group showed persistent mixed chimerism, with pathological signs of GVHD in the liver and intestine. CONCLUSIONS: Our results suggest that DLI using BM-T cells, even in small numbers, is more potent at inducing chimeric conversion in mixed chimerism than DLI using SP-T cells. Further study is needed to determine whether cryopreserved BM-T cells are an effective cell source for DLI to consolidate donor-dominant chimerism in clinical practice without concerns about GVHD.

Dendritic cells and antigen trapping technology--a revolution in vaccine/immunotherapy strategy.

Vaccines based on dendritic cells--the immune system's key responders to foreign invaders--grabbed the spotlight of this decade. Scientists have devised a dozen different ways to make dendritic cell vaccines. They have linked dendritic cells with all kinds of antigens, including peptides derived from gene mutations, tumor/pathogen RNA, viral vectors, and with whole pathogen/tumor lysate. And they are adding cytokines such as granulocyte macrophage colony stimulating factor or interleukin 4 during dendritic cell growth or maturation or at the site of vaccination to try to boost response. We are still learning the best way to generate the dendritic cells, load them with the antigen and send them to the right place in the body, and use of the biological stage of development of dendritic cells that is best suited to stimulate a response. In the present review attempts have been made to present a comprehensive synopsis of the history, development and ramifications of evolving knowledge on dendritic cell biology and the prospects for being developed as a rational immunotherapeutic tool. Further clinical studies are warranted.

Evolution and conservation of immunological activity

Paraphrasing what Gregory Bateson says on evolution, we might say that: "Immunology has long been badly taught. In particular, students - and even professional immunologists - acquire theories of immunological activity without any deep understanding of what problems these theories attempt to solve."

Células T reguladoras, infección y autoinmunidad: implicaciones en terapéutica / Regulatory T cells, Infection and Autoimmunity. Therapeutic implications

El entendimiento del equilibrio del sistema inmune es, además de una pregunta aún no resuelta, una esperanza para el principio de la terapéutica en enfermedades que le siguen ganando la batalla al ejercicio médico. La respuesta inmune innata permite la diferenciación de lo propio y lo extraño mediante receptores de reconocimiento de patrones moleculares asociados a patógenos que activan las células presentadoras de antígeno cuando se unen con moléculas estructural y químicamente conservadas entre los patógenos. Sin embargo, el sistema inmune se torna tan complejo que estos controles iniciales no son suficientes para un funcionamiento perfecto. La presencia de enfermedades autoinmunes continúa sin una explicación absoluta y la señal de cuándo apagar una respuesta inmune no está completamente entendida hasta ahora. El redescubrimiento de las células T reguladoras satisface no sólo explicaciones del equilibrio inmune sino que también se convierte en un blanco terapéutico muy seductor para el anhelado control de la respuesta inflamatoria, fenómenos infecciosos y autoinmunes. Consecuente con esto, la célula T reguladora explicaría cómo las infecciones que estimulan su proliferación puedan ser protectoras de autoinmunidad independiente de la carga genética o medio ambiente en que se desarrolle el individuo. Las infecciones que, por el contrario, eliminen o inactiven las células T reguladoras, favorecen la presencia de autoinmunidad. Se consultaron únicamente artículos en inglés o español en la bases de datos PubMed hasta la fecha de envío del artículo.

The mechanisms underlying the control of the immune system are still incompletely solved. The treatment of many human diseases is still a medical challenge. The innate immune system recognizes the difference between self and non-self antigens through the binding of pathogen associated molecular patterns to pattern recognition receptors present on the antigen presenting cells. The recent rediscovered regulatory T cells participate in the immune system homeostasis. On the other hand, regulatory T cells may be incriminated in the pathology of both inflammatory and infectious diseases. Thus, these cells would be a suitable target for the treatment of diseases in which they are involved. The participation of regulatory T cells in some infectious diseases could explain why there is an opposite association between some infectious diseases such as tuberculosis and autoimmune diseases. As a corollary, depletion or inactivation of regulatory T cells could facilitate the development of autoimmune phenomena.

Producción de interferón gamma por linfocitos pas-positivos infiltrados en corazones de pacientes chagasicos en los sitos de lesiones / Interferon gamma production by pas-positive T Lymphocytes of chagastic patients infiltrated into human hearts in the sites of lesions

En sangre de chagásicos en trabajos previos se halló un número alto de linfocitos T productores de substancia P.A.S.- positiva, más numerosos en chagásicos con electrocardiograma anormal. Luego los hallamos infiltrados en el corazón chagásico. En este trabajo consideramos nuestra hipótesis de que esa substancia linfocitaria sería Interferongamma. Material y Métodos. Muestras de corazones de 8 chagásicos fallecidos por muerte cardiaca. Se utilizaron anticuerpos monoclonales anti-IFN gamma humano; para linfocitos T activados (CD45 ROJ, y la reacción del P.A.S, respectivamente. Las células positivas se contaron en 50 campos a 400x y el estado de miocardio se comparó con datos clínicos. También. en frotis de sangre de pacientes chagásicos con ECG anormal, investigamos inmunomarcación con anti interferon gamma y la P.A.S.-positividad, respectivamente. Resultados El mayor número de células infiltrantes intracardiacas (65-75%) resultaron positivos para IFN gamma, y similares valores para P.A.S.-positividad y para CD45 RO. En sangre hallamos 41 % ±7 de linfocitos P.A.S.-positivos: y similar de positivos para IFN-gamma. Conclusiones: Los datos muestran que los linfocitos P.A.S.-positivos de los chagásicos producen IFN-gamma tanto en sangre. Como infiltrados en tejidos cardíacos. e indican una fuerte respuesta T-helper l. También explican la gran afluencia de macrófagos en dichos tejidos cardíacos. No se vieron parásitos T. cruzi ni formas intracelulares. Esos hechos refuerzan los datos que indican existencia de autoinmunidad en Chagas. Abrimos una pregunta: ¿a que antígeno/s responden en el corazón chagásico los linfocitos T P.A.S.-positivos productores de IFN-gamma?

In the blood of chagasic patients, a high number of T-lymphocytes producers of a P.A.S.-positive substance was found, more numerous in chagasics with abnormal electrocardiogram. Further. We found such lymphocytes infiltrated in the chagasic heart. Here, we considered our hypothesis that those lymphocytes would be Interferon -gamma producer' cells. Material and Methods: Heart samples of 8 patients deceased due to chagasic heart disease (ChHD). Cuts of 5 microns were submitted to monoclonal antibodies for human Interferon-gamma; to CD45RO for activated T lymphocytes; and to the classical Periodic acid Schiff reaction (P.A.S.), respectively. In blood smears from chagasic patients with ChHD, the reactivity for anti Interferon gamma and for the P.A.S. reaction was compared, regarding the respective positive cell number. The myocardium status was compared with clinical date. Results: In hearts, 65-75% of infiltrated lymphocytes were positive for IFN-gamma; similar values were found, in seriated cuts, of P.A.S.-positive lymphocytes, as well as of CD45RO+. In blood, there were 41 % ±9 of P.A.S.positive lymphocytes, similar to positive cells for IFN-gamma. Conclusions: The data indicates that the P.A.S.-positive lymphocytes from chagasic patients are producers of IFN gamma in blood, as well as when infiltrated into the cardiac tissues. Such fact explains also the great affluence of macrophages in cardiac tissues in ChHD. The data indicate a strong response of T helper 1 type in this severe advanced stage of Chagas'disease. Either Trypanosome cruzi parasites or intracellular forms were seen in these hearts. This favours the data showing autoimmune mechanisms in this process. We open a question: to which antigen/s respond in the chagasic hearts the lymphocytes producers of IFN gamma?

Interacción entre proteínas y glicanos en la regulación fisiológica de las células T / How do protein-glycan interactions regulate T-cell physiology?

Recent evidence indicates that protein-glycan interactions play a critical role in different events associated with the physiology of T-cell responses including thymocyte maturation, T-cell activation, lymphocyte migration and T-cell apoptosis. Glycans decorating T-cell surface glycoproteins can modulate T-cell physiology by specifically interacting with endogenous lectins including selectins and galectins. These endogenous lectins are capable of recognizing sugar structures localized on T-cell surface glycoproteins and trigger different signal transduction pathways leading to differentiation, proliferation, cell cycle regulation or apoptosis. Protein-carbohydrate interactions may be controlled at different levels, including regulated expression of lectins during T-cell maturation and differentiation and the spatio-temporal regulation of glycosyltransferases and glycosidases, which create and modify sugar structures present in T-cell surface glycoproteins. This article briefly reviews the mechanisms by which protein-carbohydrate interactions modulate immunological processes such as T-cell activation, migration and apoptosis.

Las interacciones entre proteínas y glicanos juegan un papel fundamental en numerosos eventos de la regulación de la fisiología del sistema inmune, como maduración tímica, activación, migración y apoptosis de células T. Los carbohidratos son capaces de modular la fisiología linfocitaria a través de la interacción específica con lectinas endógenas como selectinas y galectinas. Estas lectinas endógenas son capaces de reconocer estructuras sacarídicas localizadas en glicoproteínas de la superficie celular y regular procesos tan diversos como proliferación, diferenciación y ciclo celular. Existen diversos niveles de control de la interacción entre lectinas y azúcares; en primer lugar podemos mencionar la expresión regulada de estas lectinas durante el desarrollo de una respuesta inmune, y en segundo lugar la regulación espacio-temporal de la actividad de glicosiltranferasas y glicosidasas cuya función es crear y modificar los azúcares específicos para estas lectinas. Existen evidencias de que la expresión y actividad de estas enzimas se regulan en forma positiva o negativa durante diferentes eventos del desarrollo, ejecución y finalización de la respuesta inmune. En este artículo se analizarán los mecanismos a través de los cuales las interacciones entre lectinas con sus carbohidratos específicos modulan en forma específica diversos procesos fisiológicos, como maduración de timocitos, migración linfocitaria, activación y diferenciación de células T y apoptosis.

Replication of herpes simplex virus in T lymphocytes.

HSV is known to cause infection at various parts in the human body such as skin, mouth, eyes, genital area, and brain. In this study, the authors showed the possibility of HSV replication in Jurkat, a human leukemic T lymphocytes. Although the yield production was very low when compared to the other 2 epithelial cells, Vero and HEp-2 cells, the yield production could enhance after PHA activation. Delayed viral protein expression was observed in Jurkat cells. This might be the reason for low production. However, the exactly mechanism is unknown. Replication of viruses have been examined in a number of cell systems and the duration of successive steps in the replication cycle depends upon the types of cells, the virus strain, and the multiplicity of infection.

Effect of Ultraviolet Light on the Expression of Adhesion Molecules and T Lymphocyte Adhesion to Human Dermal Microvascular Endothelial Cells

In order to determine the effect of ultraviolet radiation (UVR) on the cell adhesion molecules expressed in human dermal microvascular endothelial cells (HDMEC), the cells were exposed to varying UVR doses and the cell surface was examined for expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM- 1), and E-selectin. The effect of UVB irradiation on the binding of T lymphocytes to HDMEC was also examined. UVA irradiation did not affect the surface expression of ICAM-1, VCAM-1, or E-selectin on the HDMEC. However, following UVB exposure, ELISA demonstrated a significant increase in the baseline ICAM-1 cell surface expression on the HDMEC. However, no induction of either E-selectin or VCAM-1 was noted. UVB also significantly augmented ICAM-1 induction by IL-1 alpha and TNF- alpha. VCAM-1 was induced by stimulating HDMEC with IL-1alpha following a UVB irradiation dose of 100 mJ/cm2. Flow cytometric analysis of the HDMEC stimulated with IL-1 alpha for 24h demonstrated that 12% of the cells expressed VCAM-1 but either IL-1 alpha or UVB irradiation alone failed to induce VCAM-1 expression. Enhancement of T cell-HDMEC binding by IL-1 alpha; or TNF- alpha treatment was not significantly affected after UVB irradiation. This study demonstrated that UVB irradiation can alter ICAM-1 and VCAM-1 expression on the HDMEC surface and that augmentation of ICAM-1 expression and the IL-1 alpha -dependent induction of VCAM-1 following UVB exposure might be important steps in the pathogenesis of sunburn.