The total and T. cruzi-specific CD8+ T cell compartment displays signs of immune exhaustion in chronically T. cruzi infected subjects

ALBAREDA MC; OLIVERA C; ALVAREZ M; VIOTTI R; LOCOCO B; LAUCELLA S; POSTAN M; TARLETON RL

New Orelans, USA

Congreso; American Society of Tropical Medicine and Hygiene 57th Annual Meeting; 2008

Supporting the notion that Chagas disease might progress in the presence of an ineffective immune response, previous studies from our laboratories have shown that subjects in the indeterminate stage of infection or with mild chronic heart Chagas disease have higher frequencies of T. cruzi-specific CD8+IFN-g+ T cells than subjects with severe disease. In contrast, the levels of CD8+IL-2+ T cells are low regardless the clinical status of the heart disease. This apparent impairment in CD8+ T cell responses specific for T. cruzi is also associated with an increased frequency of fully differentiated memory (CD27-CD28-CD45RA-) cells and a high rate of apoptosis in the total CD8+ T cell population, possibly reflecting a progressive exhaustion in the CD8+ T cell compartment in these subjects. Herein, we have phenotyped T. cruzi specific and total CD8+ T cells for additional markers of immune exhaustion. We found that the frequency of IFN-g+-producing CD8+ T cells with a CD27+CD28+ (early differentiation) phenotype inversely correlated with the expression of CD57 (a marker of senescence). Analysis of the total CD8+ T cell compartment showed that chronic chagasic patients with more severe clinical disease have increased percentages of CD8+ T cells expressing CD57 irrespective of the differention status of the cells and of the clinical status of the subject. The expression of the receptor for IL-7 (CD127) was also lower in the naïve CD8+ T cell compartment of patients with clinical disease while the number of T cells expressing caspase-3 in the naïve, memory and effector CD8+ T cell compartment of chronic chagasic patients was increased. Taken together, these data demonstrate that the CD8+ T cell compartment of chronic chagasic patients displays features characteristic of senescence. The diminished expression of IL-7R could contribute to the inability to maintain the memory T cell pool in persistent T. cruzi infection.