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Costimulation via OX40L Expressed by B Cells Is Sufficient to Determine the Extent of Primary CD4 Cell Expansion and Th2 Cytokine Secretion In Vivo

The development of effector and memory CD4 cell populations depends upon both T cell receptor (TCR) engagement of peptide/major histocompatibility complex (MHC) class II complexes and ligation of costimulatory molecules with counter receptors on antigen-presenting cells (APCs). We showed previously...

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Autores principales: Linton, Phyllis-Jean, Bautista, Beverly, Biederman, Elana, Bradley, Evan S., Harbertson, Judith, Kondrack, Robyn M., Padrick, Ryan C., Bradley, Linda M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193894/
https://www.ncbi.nlm.nih.gov/pubmed/12668647
http://dx.doi.org/10.1084/jem.20021290
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author Linton, Phyllis-Jean
Bautista, Beverly
Biederman, Elana
Bradley, Evan S.
Harbertson, Judith
Kondrack, Robyn M.
Padrick, Ryan C.
Bradley, Linda M.
author_facet Linton, Phyllis-Jean
Bautista, Beverly
Biederman, Elana
Bradley, Evan S.
Harbertson, Judith
Kondrack, Robyn M.
Padrick, Ryan C.
Bradley, Linda M.
author_sort Linton, Phyllis-Jean
collection PubMed
description The development of effector and memory CD4 cell populations depends upon both T cell receptor (TCR) engagement of peptide/major histocompatibility complex (MHC) class II complexes and ligation of costimulatory molecules with counter receptors on antigen-presenting cells (APCs). We showed previously that sustained interactions with APCs could be crucial for optimal expansion of CD4 cells and for development of effectors that secrete cytokines associated with Th2 cells. Using an adoptive transfer model with TCR transgenic CD4 cells, we now show that responses of CD4 cells primed in B cell–deficient mice become aborted, but are fully restored upon the transfer of activated B cells. Although B cells have the capacity to secrete multiple cytokines that could affect CD4 priming, including IL-4, we were unable to distinguish a role for cytokines that are secreted by B cells. However, B cell costimulation via the OX40L/OX40 pathway that has been implicated in CD4 cell expansion, survival, and Th2 development was required. Th2 but not Th1 responses were impaired in OX40L-deficient recipients and normal responses were restored with OX40L sufficient B cells. The results suggest that without engagement of OX40L on B cells, CD4 cell responses to many protein Ag would be dominated by Th1 cytokines. These data have important implications for strategies to achieve optimal priming of CD4 subsets.
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spelling pubmed-21938942008-04-11 Costimulation via OX40L Expressed by B Cells Is Sufficient to Determine the Extent of Primary CD4 Cell Expansion and Th2 Cytokine Secretion In Vivo Linton, Phyllis-Jean Bautista, Beverly Biederman, Elana Bradley, Evan S. Harbertson, Judith Kondrack, Robyn M. Padrick, Ryan C. Bradley, Linda M. J Exp Med Article The development of effector and memory CD4 cell populations depends upon both T cell receptor (TCR) engagement of peptide/major histocompatibility complex (MHC) class II complexes and ligation of costimulatory molecules with counter receptors on antigen-presenting cells (APCs). We showed previously that sustained interactions with APCs could be crucial for optimal expansion of CD4 cells and for development of effectors that secrete cytokines associated with Th2 cells. Using an adoptive transfer model with TCR transgenic CD4 cells, we now show that responses of CD4 cells primed in B cell–deficient mice become aborted, but are fully restored upon the transfer of activated B cells. Although B cells have the capacity to secrete multiple cytokines that could affect CD4 priming, including IL-4, we were unable to distinguish a role for cytokines that are secreted by B cells. However, B cell costimulation via the OX40L/OX40 pathway that has been implicated in CD4 cell expansion, survival, and Th2 development was required. Th2 but not Th1 responses were impaired in OX40L-deficient recipients and normal responses were restored with OX40L sufficient B cells. The results suggest that without engagement of OX40L on B cells, CD4 cell responses to many protein Ag would be dominated by Th1 cytokines. These data have important implications for strategies to achieve optimal priming of CD4 subsets. The Rockefeller University Press 2003-04-07 /pmc/articles/PMC2193894/ /pubmed/12668647 http://dx.doi.org/10.1084/jem.20021290 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Linton, Phyllis-Jean
Bautista, Beverly
Biederman, Elana
Bradley, Evan S.
Harbertson, Judith
Kondrack, Robyn M.
Padrick, Ryan C.
Bradley, Linda M.
Costimulation via OX40L Expressed by B Cells Is Sufficient to Determine the Extent of Primary CD4 Cell Expansion and Th2 Cytokine Secretion In Vivo
title Costimulation via OX40L Expressed by B Cells Is Sufficient to Determine the Extent of Primary CD4 Cell Expansion and Th2 Cytokine Secretion In Vivo
title_full Costimulation via OX40L Expressed by B Cells Is Sufficient to Determine the Extent of Primary CD4 Cell Expansion and Th2 Cytokine Secretion In Vivo
title_fullStr Costimulation via OX40L Expressed by B Cells Is Sufficient to Determine the Extent of Primary CD4 Cell Expansion and Th2 Cytokine Secretion In Vivo
title_full_unstemmed Costimulation via OX40L Expressed by B Cells Is Sufficient to Determine the Extent of Primary CD4 Cell Expansion and Th2 Cytokine Secretion In Vivo
title_short Costimulation via OX40L Expressed by B Cells Is Sufficient to Determine the Extent of Primary CD4 Cell Expansion and Th2 Cytokine Secretion In Vivo
title_sort costimulation via ox40l expressed by b cells is sufficient to determine the extent of primary cd4 cell expansion and th2 cytokine secretion in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193894/
https://www.ncbi.nlm.nih.gov/pubmed/12668647
http://dx.doi.org/10.1084/jem.20021290
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