Araujo Fernanda Fortes, Gomes Juliana Assis Silva, Rocha Manoel Otavio Costa, Williams-Blangero Sarah, Pinheiro Vladimir Martins, Morato Maria Jose Ferreira, Correa-Oliveira Rodrigo
Laboratorio de Imunologia Celular e Molecular, Centro de Pesquisas Rene Rachou-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
Front Biosci. 2007 May 1;12:2797-806. doi: 10.2741/2273.
Several immunoregulatory mechanisms are proposed to be effective both in human and experimental Trypanosoma cruzi infection. However, the role of CD4+CD25high T cells in Chagas disease has not yet been elucidated. These cells are critical for the regulation of immune response to infectious agents and in the control of autoimmune diseases. In this study, the presence of CD4+CD25high regulatory T cells in the whole blood of non-infected individuals (NI), and patients with the indeterminate (IND) and cardiac form (CARD) of Chagas disease was evaluated. To further characterize this population of regulatory cells, the co-expression of CTLA-4, CD62L, CD45RO, CD45RA, HLA-DR, CD40L, CD69, CD54, IL-10R and the intracellular molecules FOXP3 and IL-10 on the CD4+CD25high T lymphocytes was examined. FOXP3 was expressed by the majority of CD4+CD25high when compared with the other CD4+ T cells subsets in patients with Chagas disease. Patients with the IND form of the disease had a higher frequency of circulating regulatory CD4+CD25high T cells than patients with the CARD form. Moreover, there was an increase in CD4+CD25highFOXP3+ cells that were also IL-10+ in the IND group whereas, in the CARD group, there was an increase in the percentage of CD4+CD25high FOXP3+ cells that expressed CTLA-4. These data suggest that IL-10 produced by regulatory T cells is effective in controlling disease development in patients with the IND form. However, in individuals with the CARD form of the disease, the same regulatory mechanism, mediated by IL-10 and CTLA-4 expression is not sufficient to control the progression of the disease. The data suggest that CD4+CD25highFOXP3+ regulatory T cells in patients with Chagas disease might play a role in the immune response against T. cruzi infection although with distinct effects in patients with the IND and CARD forms of disease.
有几种免疫调节机制被认为在人类和实验性克氏锥虫感染中均有效。然而，CD4+CD25high T细胞在恰加斯病中的作用尚未阐明。这些细胞对于调节针对感染因子的免疫反应以及控制自身免疫性疾病至关重要。在本研究中，评估了未感染个体（NI）以及恰加斯病不确定型（IND）和心脏型（CARD）患者全血中CD4+CD25high调节性T细胞的存在情况。为了进一步表征这一调节性细胞群体，检测了CTLA-4、CD62L、CD45RO；CD45RA、HLA-DR、CD40L、CD69、CD54、IL-10R以及细胞内分子FOXP3和IL-10在CD4+CD25high T淋巴细胞上的共表达情况。与恰加斯病患者的其他CD4+ T细胞亚群相比，大多数CD4+CD25high细胞表达FOXP3。IND型疾病患者循环调节性CD4+CD25high T细胞的频率高于CARD型患者。此外，IND组中CD4+CD25highFOXP3+且也是IL-10+的细胞有所增加，而在CARD组中，表达CTLA-4的CD4+CD25high FOXP3+细胞百分比有所增加。这些数据表明，调节性T细胞产生的IL-10在控制IND型患者的疾病发展方面有效。然而，在患有CARD型疾病的个体中，由IL-10和CTLA-4表达介导的相同调节机制不足以控制疾病进展。数据表明，恰加斯病患者中的CD4+CD25highFOXP3+调节性T细胞可能在针对克氏锥虫感染的免疫反应中发挥作用，尽管在IND型和CARD型疾病患者中具有不同的作用。
