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

<div><p>Background</p><p>Adults with chronic <i>Trypanosoma cruzi</i> 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.</p><p>Methodology/Principal Findings</p><p>To test this hypothesis, the quality and magnitude of <i>T. cruzi</i>-specific T cell responses were evaluated in <i>T. cruzi</i>-infected children and compared with long-term <i>T. cruzi</i>-infected adults with no evidence of heart failure. The phenotype of CD4⁺ T cells was also assessed in <i>T. cruzi</i>-infected children and uninfected controls. Simultaneous secretion of IFN-γ and IL-2 measured by ELISPOT assays in response to <i>T. cruzi</i> antigens was prevalent among <i>T. cruzi</i>-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 <i>T. cruzi</i> showed polyfunctional T cell responses in most <i>T. cruzi</i>-infected children. Monofunctional T cell responses and an absence of CD4⁺TNF-α⁺-secreting T cells were observed in <i>T. cruzi</i>-infected adults. A relatively high degree of activation and differentiation of CD4⁺ T cells was evident in <i>T. cruzi</i>-infected children.</p><p>Conclusions/Significance</p><p>Our observations are compatible with our initial hypothesis that persistent <i>T. cruzi</i> infection promotes eventual exhaustion of immune system, which might contribute to disease progression in long-term infected subjects.</p>