Presence of antigen-experienced T cells with low grade of differentiation and proliferative potential in chronic Chagas disease myocarditis.
Presence of antigen-experienced T cells with low grade of differentiation and proliferative potential in chronic Chagas disease myocarditis.
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DOI：
10.1371/journal.pntd.0002989
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发表时间：
2014-08
影响因子：
3.8
通讯作者：
Laucella SA
中科院分区：
文献类型：
--
作者：
Argüello RJ;Vigliano C;Cabeza-Meckert P;Viotti R;Garelli F;Favaloro LE;Favaloro RR;Laguens R;Laucella SA
慢性克氏锥虫感染的主要后果是在大约20-30%的感染个体中发生心肌炎，但直到初始感染后10-20年才发生。我们先前已经表明，在慢性恰加斯病患者中，对克氏锥虫抗原有应答的循环干扰素-γ-分泌T细胞显示出低分化，并且这些T淋巴细胞的频率随着心脏病的严重程度沿着降低。本研究旨在探讨晚期恰加斯病心肌炎患者心脏组织中抑制性受体、1型或调节性T细胞转录因子、T细胞分化、免疫衰老或细胞周期活跃标志物的表达。通过免疫组织化学和免疫荧光技术评价了接受心脏移植的晚期慢性恰加斯病患者心脏外植体中T和B细胞以及巨噬细胞的不同标志物的表达。大多数浸润细胞显示抗原经历的T细胞（CD 3+、CD 4+、CD 8+、CD 45 RO+）的标志物，分化程度较低（CD 27+、CD 57 −、CD 45 RA −、PD-1−）。T-bet表达支持T辅助细胞1/T细胞毒性细胞1的偏态分布;而FOXP 3+细胞稀少，仅位于严重心肌炎的区域。此外，Ki 67染色显示，慢性克氏锥虫感染患者的CD 3 + T细胞增殖能力显著增强，T细胞反应的质量和免疫调节机制可能决定了慢性克氏锥虫感染患者的细胞反应模式和疾病的严重程度。查加斯病是一种被忽视的热带疾病，影响着世界上大约1 000万人。它是由原生动物克氏锥虫感染引起的。由于移民流动，该疾病也在非流行国家流行。在这项研究中，通过分析抑制性受体、1型或调节性T细胞的转录因子以及T细胞分化、免疫衰老或活性细胞周期的标志物的表达，评估了终末期慢性恰加斯病患者心脏组织中炎性T细胞的功能和表型特征。大多数浸润细胞显示抗原经历的T细胞的标记物，具有低分化和显著的增殖能力。T-bet表达支持T辅助细胞1/T细胞毒性细胞1的偏态分布，而FOXP 3+细胞很少。T细胞应答的质量和免疫调节机制可能决定克氏锥虫感染的细胞应答模式和疾病的严重程度。
The main consequence of chronic Trypanosoma cruzi infection is the development of myocarditis in approximately 20–30% of infected individuals but not until 10–20 years after the initial infection. We have previously shown that circulating interferon-γ-secreting T cells responsive to Trypanosoma cruzi antigens in chronic Chagas disease patients display a low grade of differentiation and the frequency of these T lymphocytes decreases along with the severity of heart disease. This study thought to explore the expression of inhibitory receptors, transcription factors of type 1 or regulatory T cells, and markers of T cell differentiation, immunosenescence or active cell cycle in cardiac explants from patients with advanced Chagas disease myocarditis. The expression of different markers for T and B cells as well as for macrophages was evaluated by immunohistochemistry and immunofluorescence techniques in cardiac explants from patients with advanced chronic Chagas disease submitted to heart transplantation. Most infiltrating cells displayed markers of antigen-experienced T cells (CD3+, CD4+, CD8+, CD45RO+) with a low grade of differentiation (CD27+, CD57−, CD45RA−, PD-1−). A skewed T helper1/T cytotoxic 1 profile was supported by the expression of T-bet; whereas FOXP3+ cells were scarce and located only in areas of severe myocarditis. In addition, a significant proliferative capacity of CD3+ T cells, assessed by Ki67 staining, was found. The quality of T cell responses and immunoregulatory mechanisms might determine the pattern of the cellular response and the severity of disease in chronic Trypanosoma cruzi infection. Chagas disease is a neglected tropical disease affecting approximately 10 million people in the world. It is caused by infection with the protozoan Trypanosoma cruzi. As a consequence of migration flows, the disease has been also become established in non-endemic countries. In this study, the functional and phenotypic profile of inflammatory T cells were evaluated in heart tissues of patients with end-stage chronic Chagas disease by analyzing the expression of inhibitory receptors, transcription factors of type 1 or regulatory T cells, and markers of T cell differentiation, immunosenescence or active cell cycle. Most infiltrating cells displayed markers of antigen-experienced T cells with a low grade of differentiation and a significant proliferative capacity. A skewed T helper1/T cytotoxic 1 profile was supported by the expression of T-bet; whereas FOXP3+ cells were scarce. The quality of T cell responses and immunoregulatory mechanisms might determine the pattern of the cellular response and the severity of disease in Trypanosoma cruzi infection.
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来自跨硅酸盐酶蛋白的HLA I-T类细胞表位在慢性chagas病中揭示了CD8+ T细胞的功能不同的子集。
影响因子：
3.8
作者：
Alvarez MG;Postan M;Weatherly DB;Albareda MC;Sidney J;Sette A;Olivera C;Armenti AH;Tarleton RL;Laucella SA
通讯作者：
Laucella SA
影响因子：
3.1
作者：
Gomes, JAS;Bahia-Oliveira, LMG;Correa-Oliveira, R
通讯作者：
Correa-Oliveira, R
影响因子：
158.5
作者：
Cooper, LT;Berry, GJ;Shabetai, R
通讯作者：
Shabetai, R
影响因子：
4.4
作者：
Albareda, MC;Laucella, SA;Postan, M
通讯作者：
Postan, M
影响因子：
3.8
作者：
de Melo, Adriene Siqueira;Barros de Lorena, Virginia Maria;Gomes, Yara de Miranda
通讯作者：
Gomes, Yara de Miranda