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ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS

The co-stimulatory molecule ICOS is associated with the induction and regulation of T helper cell responses, including the differentiation of follicular helper T (Tfh) cells and the formation and maintenance of memory T cells. However, the role of ICOS signaling in secondary immune responses is larg...

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Autores principales: Latham, Leah E., Wikenheiser, Daniel J., Stumhofer, Jason S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213745/
https://www.ncbi.nlm.nih.gov/pubmed/32348365
http://dx.doi.org/10.1371/journal.ppat.1008527
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author Latham, Leah E.
Wikenheiser, Daniel J.
Stumhofer, Jason S.
author_facet Latham, Leah E.
Wikenheiser, Daniel J.
Stumhofer, Jason S.
author_sort Latham, Leah E.
collection PubMed
description The co-stimulatory molecule ICOS is associated with the induction and regulation of T helper cell responses, including the differentiation of follicular helper T (Tfh) cells and the formation and maintenance of memory T cells. However, the role of ICOS signaling in secondary immune responses is largely unexplored. Here we show that memory T cell formation and maintenance are influenced by persistent infection with P. chabaudi chabaudi AS infection, as memory T cell numbers decline in wild-type and Icos(-/-) mice after drug-clearance. Following drug-clearance Icos(-/-) mice display a relapsing parasitemia that occurs more frequently and with higher peaks compared to wild-type mice after re-challenge. The secondary immune response in Icos(-/-) mice is characterized by significant impairment in the expansion of effector cells with a Tfh-like phenotype, which is associated with a diminished and delayed parasite-specific Ab response and the absence of germinal centers. Similarly, the administration of an anti-ICOSL antagonizing antibody to wild-type mice before and after reinfection with P. c. chabaudi AS leads to an early defect in Tfh cell expansion and parasite-specific antibody production, confirming a need for ICOS-ICOSL interactions to promote memory B cell responses. Furthermore, adoptive transfer of central memory T (T(CM)) cells from wild-type and Icos(-/-) mice into tcrb(-/-) mice to directly evaluate the ability of T(CM) cells to give rise to Tfh cells revealed that T(CM) cells from wild-type mice acquire a mixed Th1- and Tfh-like phenotype after P. c. chabaudi AS infection. While T(CM) cells from Icos(-/-) mice expand and display markers of activation to a similar degree as their WT counterparts, they displayed a reduced capacity to upregulate markers indicative of a Tfh cell phenotype, resulting in a diminished humoral response. Together these findings verify that ICOS signaling in memory T cells plays an integral role in promoting T cell effector responses during secondary infection with P. c. chabaudi AS.
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spelling pubmed-72137452020-05-26 ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS Latham, Leah E. Wikenheiser, Daniel J. Stumhofer, Jason S. PLoS Pathog Research Article The co-stimulatory molecule ICOS is associated with the induction and regulation of T helper cell responses, including the differentiation of follicular helper T (Tfh) cells and the formation and maintenance of memory T cells. However, the role of ICOS signaling in secondary immune responses is largely unexplored. Here we show that memory T cell formation and maintenance are influenced by persistent infection with P. chabaudi chabaudi AS infection, as memory T cell numbers decline in wild-type and Icos(-/-) mice after drug-clearance. Following drug-clearance Icos(-/-) mice display a relapsing parasitemia that occurs more frequently and with higher peaks compared to wild-type mice after re-challenge. The secondary immune response in Icos(-/-) mice is characterized by significant impairment in the expansion of effector cells with a Tfh-like phenotype, which is associated with a diminished and delayed parasite-specific Ab response and the absence of germinal centers. Similarly, the administration of an anti-ICOSL antagonizing antibody to wild-type mice before and after reinfection with P. c. chabaudi AS leads to an early defect in Tfh cell expansion and parasite-specific antibody production, confirming a need for ICOS-ICOSL interactions to promote memory B cell responses. Furthermore, adoptive transfer of central memory T (T(CM)) cells from wild-type and Icos(-/-) mice into tcrb(-/-) mice to directly evaluate the ability of T(CM) cells to give rise to Tfh cells revealed that T(CM) cells from wild-type mice acquire a mixed Th1- and Tfh-like phenotype after P. c. chabaudi AS infection. While T(CM) cells from Icos(-/-) mice expand and display markers of activation to a similar degree as their WT counterparts, they displayed a reduced capacity to upregulate markers indicative of a Tfh cell phenotype, resulting in a diminished humoral response. Together these findings verify that ICOS signaling in memory T cells plays an integral role in promoting T cell effector responses during secondary infection with P. c. chabaudi AS. Public Library of Science 2020-04-29 /pmc/articles/PMC7213745/ /pubmed/32348365 http://dx.doi.org/10.1371/journal.ppat.1008527 Text en © 2020 Latham et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Latham, Leah E.
Wikenheiser, Daniel J.
Stumhofer, Jason S.
ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS
title ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS
title_full ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS
title_fullStr ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS
title_full_unstemmed ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS
title_short ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS
title_sort icos signaling promotes a secondary humoral response after re-challenge with plasmodium chabaudi chabaudi as
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213745/
https://www.ncbi.nlm.nih.gov/pubmed/32348365
http://dx.doi.org/10.1371/journal.ppat.1008527
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