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-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. © 2013 albareda et al.