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

<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 an...

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Autores principales: María C Albareda, Ana M De Rissio, Gonzalo Tomas, Alicia Serjan, María G Alvarez, Rodolfo Viotti, Laura E Fichera, Mónica I Esteva, Daniel Potente, Alejandro Armenti, Rick L Tarleton, Susana A Laucella
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:a45df8bb769e448e918b841e2efa56f22021-11-18T09:16:35ZPolyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults.1935-27271935-273510.1371/journal.pntd.0002575https://doaj.org/article/a45df8bb769e448e918b841e2efa56f22013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24349591/?tool=EBIhttps://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<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.María C AlbaredaAna M De RissioGonzalo TomasAlicia SerjanMaría G AlvarezRodolfo ViottiLaura E FicheraMónica I EstevaDaniel PotenteAlejandro ArmentiRick L TarletonSusana A LaucellaPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 7, Iss 12, p e2575 (2013)
institution DOAJ
collection DOAJ
language EN
topic Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
spellingShingle Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
María C Albareda
Ana M De Rissio
Gonzalo Tomas
Alicia Serjan
María G Alvarez
Rodolfo Viotti
Laura E Fichera
Mónica I Esteva
Daniel Potente
Alejandro Armenti
Rick L Tarleton
Susana A Laucella
Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults.
description <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.
format article
author María C Albareda
Ana M De Rissio
Gonzalo Tomas
Alicia Serjan
María G Alvarez
Rodolfo Viotti
Laura E Fichera
Mónica I Esteva
Daniel Potente
Alejandro Armenti
Rick L Tarleton
Susana A Laucella
author_facet María C Albareda
Ana M De Rissio
Gonzalo Tomas
Alicia Serjan
María G Alvarez
Rodolfo Viotti
Laura E Fichera
Mónica I Esteva
Daniel Potente
Alejandro Armenti
Rick L Tarleton
Susana A Laucella
author_sort María C Albareda
title Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults.
title_short Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults.
title_full Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults.
title_fullStr Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults.
title_full_unstemmed Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults.
title_sort polyfunctional t cell responses in children in early stages of chronic trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/a45df8bb769e448e918b841e2efa56f2
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