Perturbed T Cell IL-7 Receptor Signaling in Chronic Chagas Disease

作者：Cecilia Albareda M; Perez Mazliah Damian; Ailen Natale M; Castro Eiro Melisa; Alvarez Maria G; Viotti Rodolfo; Bertocchi Graciela; Lococo Bruno; Tarleton Rick L; Laucella Susana A^*

来源：The Journal of Immunology, 2015, 194(8): 3883-+.

DOI：10.4049/jimmunol.1402202

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.

• 出版日期2015-4-15