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

ALBAREDA M C; PEREZ-MAZLIAH D; NATALE MA; CASTRO-EIRO M; ALVAREZ MG; VIOTTI R ; BERTOCCHI GL; LOCOCO BE; TARLETON RL ; LAUCELLA SA

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2015

0022-1767

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 CD1272CD132+ 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.