Role of the expression and functionality of the IL-7 receptor in T cell responses to Trypanosma cruzi in chronically infected subjects

ALBAREDA M. CECILIA; AILEN NATALE; ALVAREZ M; VIOTTI R; BERTOCCHI GL; LOCOCO BE; LAUCELLA S

Simposio; Cell Biology and Immunology of Persistent Infection; 2016

Supporting the notion that persistent infection with T. cruzi leads to T cell exhaustion, we have demonstrated that disease manifestation was strongly correlated with impaired functionality of the T cell compartment, decreased levels of total naïve T cells and decreased IL-7R expression. IL-7 plays an important role in the maintenance of naive and memory T cell compartments, positively regulating the survival, differentiation, and proliferation of T cells. The regulation of the two IL-7R chains is different while CD127 is downregulated upon T cell activation CD132 chain is rapidly upregulated. Recently, we have shown alterations in the signaling pathway of IL-7/IL-7R in the total T cell compartment of chronically T. cruzi-infected subjects. Herein, we study the capability of T cells to respond to T. cruzi antigens in relation to the expression of the components (CD127/CD132) and functionality of the IL-7R in patients with different clinical forms of chronic cardiac Chagas disease. A decrease in CD4+CD45RA−CD127+CD132+ and CD8+CD45RA¯CD127+CD132+ T cells in subjects with lower degree of cardiac dysfunction compared with those with severe disease was found. Subjects with positive responses to a T. cruzi lysate, measured by ELISPOT for IFN-γ and IL-2, more frequently displayed decreased frequencies of CD4+CD45RA-CD127+CD132+ T cells compared with subjects with negative responses, supporting a modulation of the IL-7R in better clinical stages. The lack of T. cruzi-specific T cell responses in subjects with cardiac symptoms was correlated with a poor functional capacity of the IL-7R, assessed by the ability of IL-7 to induce STAT5 phosphorylation and CD25 expression on T cells. These findings support a possible role in the signaling pathway of the IL-7R in maintaining T.cruzi-specific lymphocytes in the course of the chronic infection.Grant PICTO-ANLIS 2011-116.