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Background  Adults with chronic  Trypanosoma cruzi  exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN-γ-only secreting) parasite-specific T cells and increased levels of terminally differentiated T cells. It is possible that persistent infection and/or sustained exposure to parasites antigens may lead to a progressive loss of function of the immune T cells.    Methodology/Principal Findings  To test this hypothesis, the quality and magnitude of  T. cruzi -specific T cell responses were evaluated in  T. cruzi -infected children and compared with long-term  T. cruzi -infected adults with no evidence of heart failure. The phenotype of CD4 +  T cells was also assessed in  T. cruzi -infected children and uninfected controls. Simultaneous secretion of IFN-γ and IL-2 measured by ELISPOT assays in response to  T. cruzi  antigens was prevalent among  T. cruzi -infected children. Flow cytometric analysis of co-expression profiles of CD4 +  T cells with the ability to produce IFN-γ, TNF-α, or to express the co-stimulatory molecule CD154 in response to  T. cruzi  showed polyfunctional T cell responses in most  T. cruzi -infected children. Monofunctional T cell responses and an absence of CD4 + TNF-α + -secreting T cells were observed in  T. cruzi -infected adults. A relatively high degree of activation and differentiation of CD4 +  T cells was evident in  T. cruzi -infected children.    Conclusions/Significance  Our observations are compatible with our initial hypothesis that persistent  T. cruzi  infection promotes eventual exhaustion of immune system, which might contribute to disease progression in long-term infected subjects.

plos neglected tropical diseases

Polyfunctional T Cell Responses in Children in Early Stages of Chronic Trypanosoma cruzi Infection Contrast with Monofunctional Responses of Long-term Infected Adults