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

Background Adults with chronic Trypanosoma cruzi exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN--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- 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-, TNF-, 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-(+)-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. Author Summary Chagas disease is a neglected tropical disease affecting approximately 10 million people in the world. As a consequence of migration flows, the disease has also become established in non-endemic countries. Previous studies have demonstrated that Trypanosoma cruzi-specific T cells inversely correlates with the severity of cardiac disease in the chronic phase of the infection, suggesting that the immune system becomes exhausted overtime. To test this hypothesis, the quality and magnitude of T. cruzi-specific T cell responses were measured in T. cruzi-infected children - who are presumed to have shorter-term infections - and compared with long-term T. cruzi-infected adults. The activation status of total T cells in T. cruzi-infected children was also evaluated. T. cruzi-infected children exhibit a more robust, and more highly functional parasite specific T cell responses compared to T. cruzi-infected adults. In spite of a more functional immune profile, T. cruzi-infected children have a heightened state of immune activation. These observations are compatible with the initial hypothesis that T cell responses specific for T. cruzi become exhausted overtime. The impairment in T cell responses might contribute to disease progression in long-term infected subjects.