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PLoS Negl Trop Dis. 2013 Dec 12;7(12):e2575. doi: 10.1371/journal.pntd.0002575. eCollection 2013.

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

Author information

1
Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires, Argentina ; Hospital Interzonal General de Agudos Eva Perón, Buenos Aires, Argentina.
2
Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires, Argentina.
3
Hospital Fernandez, Buenos Aires, Argentina.
4
Hospital Interzonal General de Agudos Eva Perón, Buenos Aires, Argentina.
5
Center for Tropical and Emerging Global Diseases, Athens, Georgia, United States of America.

Abstract

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.

PMID:
24349591
PMCID:
PMC3861186
DOI:
10.1371/journal.pntd.0002575
[Indexed for MEDLINE]
Free PMC Article

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