Chronically Trypanosoma cruzi Infected Subjects Lacking Parasite Specific T Responses Have Alterations in the IL7/IL7R Signalling Pathway

MARIA AILEN NATALE; ALVAREZ M. GABRIELA; VIOTTI R; BERTOCHI G; LOCCOCO B; LAUCELLA S; ALBAREDA MC

Simposio; Molecular and Translational Advances in Parasitic Diseases, Gordon Research Conference; 2016

Chronically Trypanosoma cruzi Infected Subjects Lacking Parasite Specific T Responses Have Alterations in the IL7/IL7R Signalling PathwayNatale MA1, Alvarez MG2, Viotti R2, Bertocchi G2, Lococo B2, Laucella S1, Albareda MC1. 1INP ?Dr. F. Chaben? Buenos Aires, Argentina; 2 HIGA ?Eva Perón, Buenos Aires, Argentina; 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. Previous studies showed a negative correlation between the T lymphocytes functionality and the severity of chronic Chagas disease. The signalling through IL-7 receptor is important in the maintenance of memory and naive T cells compartments. The IL-7 cell surface receptor is composed of the specific IL-7Rα (CD127) chain and the common γ-chain (CD132). Upon T cell activation, CD127 chain is downregulated while CD132 is rapidly upregulated. Recently, we showed alterations in the IL-7/IL-7R pathway in the lymphocytes T compartment of those patients. In this study, we managed to address whether T. cruzi specific T cells responses correlated with the expression and functionality of the IL-7R in patients at different clinical stages of the chronic infection. Subjects who presented a positive response to a protein lysate from T. cruzi amastigotes, measured by IFN-γ/IL-2 ELISPOT, showed a decrease in the percentage of CD127+CD132+ cells and a reciprocal gain of CD127-CD132+ in CD8+ and CD4+ antigen experienced (CD45RA-) T cells, independently from the clinical stage, compared with non-responders patients and uninfected controls, showing that responders subjects are more likely to modulate IL-7R expression as expected in the context of a process of immune activation. IL-7?induced phosphorylation of STAT5 was lower in the group of patients with cardiac symptoms with lack of specific T. cruzi-T cell responses in both CD4+ and CD8+ T lymphocytes. Additionally, Bcl-2 and CD25 expression after stimulation were altered in non-responders. Moreover, non-responders showed a lower level of CD4+ naive T lymphocytes. In conclusion, these results highlight a possible role of the IL-7/IL-7R pathway on the maintenance of the parasite-specific T lymphocytes during the infection.