Albareda M Cecilia, Perez-Mazliah Damián, Natale M Ailén, Castro-Eiro Melisa, Alvarez María G, Viotti Rodolfo, Bertocchi Graciela, Lococo Bruno, Tarleton Rick L, Laucella Susana A
Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires 1063, Argentina; Hospital Interzonal General de Agudos Eva Perón, 1650 San Martin, Buenos Aires, Argentina; and.
Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires 1063, Argentina;
J Immunol. 2015 Apr 15;194(8):3883-9. doi: 10.4049/jimmunol.1402202. Epub 2015 Mar 13.
We have previously demonstrated that immune responses in subjects with chronic Trypanosoma cruzi infection display features common to other persistent infections with signs of T cell exhaustion. Alterations in cytokine receptor signal transduction have emerged as one of the cell-intrinsic mechanisms of T cell exhaustion. In this study, we performed an analysis of the expression of IL-7R components (CD127 and CD132) on CD4(+) and CD8(+) T cells and evaluated IL-7-dependent signaling events in patients at different clinical stages of chronic chagasic heart disease. Subjects with no signs of cardiac disease showed a decrease in CD127(+)CD132(+) cells and a reciprocal gain of CD127(-)CD132(+) in CD8(+) and CD4(+) T cells compared with either patients exhibiting heart enlargement or uninfected controls. T. cruzi infection, in vitro, was able to stimulate the downregulation of CD127 and the upregulation of CD132 on T cells. IL-7-induced phosphorylation of STAT5 as well as Bcl-2 and CD25 expression were lower in T. cruzi-infected subjects compared with uninfected controls. The serum levels of IL-7 were also increased in chronic chagasic patients. The present study highlights perturbed IL-7/IL-7R T cell signaling through STAT5 as a potential mechanism of T cell exhaustion in chronic T. cruzi infection.
我们之前已经证明，慢性克氏锥虫感染患者的免疫反应表现出与其他持续性感染共有的特征，并有T细胞耗竭的迹象。细胞因子受体信号转导的改变已成为T细胞耗竭的细胞内在机制之一。在本研究中，我们分析了慢性恰加斯心脏病不同临床阶段患者CD4(+)和CD8(+) T细胞上IL-7R成分（CD127和CD132）的表达，并评估了IL-7依赖性信号事件。与出现心脏扩大的患者或未感染的对照组相比，无心脏病迹象的受试者CD8(+)和CD4(+) T细胞中CD127(+)CD132(+)细胞减少，CD127(-)CD132(+)细胞相应增加。体外克氏锥虫感染能够刺激T细胞上CD127的下调和CD132的上调。与未感染的对照组相比，克氏锥虫感染患者中IL-7诱导的STAT5磷酸化以及Bcl-2和CD25表达较低。慢性恰加斯病患者的血清IL-7水平也升高。本研究强调，通过STAT5干扰IL-7/IL-7R T细胞信号传导是慢性克氏锥虫感染中T细胞耗竭的潜在机制。
