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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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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. |
format | Online Article Text |
id | pubmed-7213745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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