Estudo da apoptose como mecanismo de supressão induzido por células T reguladoras CD4+CD25 high FOXP3+ de pacientes nas diferentes formas clínicas da doença de Chagas

Exportado OPUSMade available in DSpace on 2019-08-09T12:36:44Z (GMT). No. of bitstreams: 1 disserta__o_mestrado_marcosdamasio_corrigida_pos_defesa.pdf: 1751394 bytes, checksum: 879d42b88445fc8f33f648f6d4dbd7d1 (MD5) Previous issue date: 23As células T CD4+CD25highFOXP3+ (Treg) foram descritas como sendo células com capacidade de controlar a resposta imune através da supressão de células apresentadoras de antígeno e células T efetoras. Vários mecanismos supressores induzidos por estas células têm sido propostos na infecção causada pelo protozoário T. cruzi como, apoptose e secreção de citocinas. Contudo, o papel das células Treg na doença de Chagas humana ainda não foi estabelecido. Diante disso, o objetivo deste trabalho foi avaliar a expressão de marcadores de apoptose em células T reguladoras CD4+CD25highFOXP3+ de pacientes com as formas clínicas IND e CARD (CCV). Para isso, foram coletadas amostras de sangue periférico de pacientes com as formas clínicas indeterminada (IND) e cardíaca (CARD) e em seguida avaliada a frequência de células T CD4+CD25highFOXP3+, bem como a expressão das seguintes moléculas de superfície e intracitoplasmáticas por estas células: CD39, CD95, CD95L, PD1, PD-1L e IL-17. O sangue de indivíduos não infectados (NI) foi utilizado como controle. Os resultados confirmaram a maior frequência de células T CD4+CD25highFOXP3+ em pacientes do grupo IND do que em pacientes dos grupos CARD e NI. A avaliação da expressão de CD39 e CD95L pelas células Treg, indicou maior expressão destas moléculas em pacientes do grupo IND se comparado com pacientes do grupo CARD ou NI. Já as células Treg de pacientes do grupo CARD apresentaram maior intensidade média de fluorescência para o receptor CD95 do que as células Treg de pacientes dos grupos IND ou NI. Observamos também correlação positiva na expressão das moléculas PD1 e PD1-L na superfície das células Treg de pacientes do grupo CARD. Com relação à expressão IL-17, os resultados mostraram maior frequência de células T CD4+CD25highFOXP3+IL-17+ em pacientes do grupo IND. Por fim, identificamos que os monócitos são as células que mais sofrem apoptose em todos os grupos estudados. Diante disso, os dados permitiram concluir que a citocina IL-17 possui provavelmente papel importante no desenvolvimento da fase crônica da doença de Chagas. Além disso, a expressão diferencial de cada molécula indutora de apoptose e seus receptores sugere que mecanismos supressores distintos possam estar atuando em cada forma clínica da doença de chagas.The regulatory T cells CD4+CD25highFOXP3+ (Treg) were described as cells with the capacity to control the immune response through the supression of antigen presenting cells and effector T cells. Many mechanisms induced by these cells have been proposed in the T. cruzi infection, as apoptosis and cytokines secretion. However, the role of Treg cells in human Chagas disease is not stablished yet. Then, the aim of this study was to evaluate the expression of apoptotic molecules in regulatory T cells CD4+CD25highFOXP3+ of patients with the clinical forms IND and CARD (CCCV). Thereunto, peripheral blood samples of patients with indeterminate form (IND) and cardiac form (CARD) were collected. Posteriorly, we evaluate the frequency of T cells CD4+CD25highFOXP3+, as well as the expression of the following surface and intracitoplasmic molecules: CD39, CD95, CD95L, PD1, PD-1L e IL-17. Peripheral blood samples of non-infected individuals (NI) were used as control. The results confirmed the higher frequency of T cells CD4+CD25highFOXP3+ in patients of IND group than CARD and NI groups. The evaluation of CD39 and CD95L expression by Treg cells, showed higher expression of those molecules in patients of IND group than patients of CARD or NI groups. However, Treg cells of CARD patients presented higher mean intensity of fluorescence related to CD95 expression than Treg of IND or NI patients. We observed positive correlation in the expression of both PD1 and PD1-L in the surface of Treg of CARD patients. The results also showed higher frequency of T cells CD4+CD25highFOXP3+IL-17+ in patients of the IND group. After all, we identified monocytes as the main cells that undergo apoptosis in the different studied groups. In conclusion, the secretion of IL-17 is probably important in the development of chronic phase of Chagas disease. Moreover, the differential expression of each apoptosis-inducing molecule and their receptors suggest that distinct mechanisms may be presented in each clinical form of Chagas disease

Plasma Cytokine Expression Is Associated with Cardiac Morbidity in Chagas Disease

Submitted by Nuzia Santos ([email protected]) on 2015-02-06T13:25:14Z No. of bitstreams: 1 2014_048.pdf: 2077033 bytes, checksum: 5c9786393949bf065beeeb0aad05f1bd (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-02-06T13:25:21Z (GMT) No. of bitstreams: 1 2014_048.pdf: 2077033 bytes, checksum: 5c9786393949bf065beeeb0aad05f1bd (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-02-06T14:27:57Z (GMT) No. of bitstreams: 1 2014_048.pdf: 2077033 bytes, checksum: 5c9786393949bf065beeeb0aad05f1bd (MD5)Made available in DSpace on 2015-02-06T14:27:57Z (GMT). No. of bitstreams: 1 2014_048.pdf: 2077033 bytes, checksum: 5c9786393949bf065beeeb0aad05f1bd (MD5) Previous issue date: 2014Universidade Federal de Minas Gerais. Faculdade de Medicina. Infectologia e Medicina Tropical. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Infectologia e Medicina Tropical. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Morfologia. Belo Horizonte, Minas Gerais, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Morfologia. Belo Horizonte, Minas Gerais, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Morfologia. Belo Horizonte, Minas Gerais, BrazilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Infectologia e Medicina Tropical. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Morfologia. Belo Horizonte, Minas Gerais, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil/Instituto Nacional de Ciencia e Tecnologia em Doenças Tropicais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Infectologia e Medicina Tropical. Belo Horizonte, MG, BrazilThe expression of immune response appears to be associated with morbidity in Chagas disease. However, the studies in this field have usually employed small samples of patients and statistical analyses that do not consider the wide dispersion of cytokine production observed in these patients. The aim of this study was to evaluate the plasma cytokine levels in welldefined clinical polar groups of chagasic patients divided into categories that better reflect the wide cytokine profile and its relationship with morbidity. Patients infected with Trypanosoma cruzi (T. cruzi) were grouped as indeterminate (IND) and cardiac (CARD) forms ranging from 23 to 69 years of age (mean of 45.6611.25). The IND group included 82 individuals, ranging from 24 to 66 years of age (mean of 39.6610.3). The CARD group included 94 patients ranging from 23 to 69 years of age (mean of 48612.52) presenting dilated cardiomyopathy. None of the patients have undergone chemotherapeutic treatment, nor had been previously treated for T. cruzi infection. Healthy non-chagasic individuals, ranging from 29 to 55 years of age (mean of 42.668.8) were included as a control group (NI). IND patients have a higher intensity of interleukin 10 (IL-10) expression when compared with individuals in the other groups. By contrast, inflammatory cytokine expression, such as interferon gamma (IFN-c), tumor necrosis factor alpha (TNF-a), interleukin 6 (IL-6), and interleukin 1 beta (IL-1b), proved to be the highest in the CARD group. Correlation analysis showed that higher IL-10 expression was associated with better cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Altogether, these findings reinforce the concept that a fine balance between regulatory and inflammatory cytokines represents a key element in the establishment of distinct forms of chronic Chagas disease

Resumos concluídos - Neurociências

Resumos concluídos -  Neurociência