Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults.

• Main Authors: María C Albareda (Author), Ana M De Rissio (Author), Gonzalo Tomas (Author), Alicia Serjan (Author), María G Alvarez (Author), Rodolfo Viotti (Author), Laura E Fichera (Author), Mónica I Esteva (Author), Daniel Potente (Author), Alejandro Armenti (Author), Rick L Tarleton (Author), Susana A Laucella (Author)
• Format: Book
• Published: Public Library of Science (PLoS), 2013-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1935-2727; 1935-2735; 10.1371/journal.pntd.0002575
• Keywords: Arctic medicine. Tropical medicine; RC955-962; Public aspects of medicine; RA1-1270
• Source: PLoS Neglected Tropical Diseases, Vol 7, Iss 12, p e2575 (2013)

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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.