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Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses

With increasing age, the ability to produce protective antibodies in response to immunization declines, leading to a reduced efficacy of vaccination in the elderly. To examine the effect of age on the cognate function of CD4 T cells, we have used a novel adoptive transfer model that allows us to com...

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Autores principales: Eaton, Sheri M., Burns, Eve M., Kusser, Kimberly, Randall, Troy D., Haynes, Laura
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211991/
https://www.ncbi.nlm.nih.gov/pubmed/15611289
http://dx.doi.org/10.1084/jem.20041395
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author Eaton, Sheri M.
Burns, Eve M.
Kusser, Kimberly
Randall, Troy D.
Haynes, Laura
author_facet Eaton, Sheri M.
Burns, Eve M.
Kusser, Kimberly
Randall, Troy D.
Haynes, Laura
author_sort Eaton, Sheri M.
collection PubMed
description With increasing age, the ability to produce protective antibodies in response to immunization declines, leading to a reduced efficacy of vaccination in the elderly. To examine the effect of age on the cognate function of CD4 T cells, we have used a novel adoptive transfer model that allows us to compare identical numbers of antigen-specific naive T cells from young and aged TCR transgenic (Tg) donors. Upon transfer of aged donor CD4 T cells to young hosts, there was significantly reduced expansion and germinal center (GC) differentiation of the antigen-specific B cell population after immunization. This reduced cognate helper function was seen at all time points and over a wide range of donor cell numbers. In hosts receiving aged CD4 cells, there were also dramatically lower levels of antigen-specific IgG. These age-related defects were not due to defects in migration of the aged CD4 T cells, but may be attributable to reduced CD154 (CD40L) expression. Furthermore, we found that there was no difference in B cell expansion and differentiation or in IgG production when young CD4 T cells were transferred to young or aged hosts. Our results show that, in this model, age-related reductions in the cognate helper function of CD4 T cells contribute significantly to defects in humoral responses observed in aged individuals.
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spelling pubmed-22119912008-03-11 Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses Eaton, Sheri M. Burns, Eve M. Kusser, Kimberly Randall, Troy D. Haynes, Laura J Exp Med Article With increasing age, the ability to produce protective antibodies in response to immunization declines, leading to a reduced efficacy of vaccination in the elderly. To examine the effect of age on the cognate function of CD4 T cells, we have used a novel adoptive transfer model that allows us to compare identical numbers of antigen-specific naive T cells from young and aged TCR transgenic (Tg) donors. Upon transfer of aged donor CD4 T cells to young hosts, there was significantly reduced expansion and germinal center (GC) differentiation of the antigen-specific B cell population after immunization. This reduced cognate helper function was seen at all time points and over a wide range of donor cell numbers. In hosts receiving aged CD4 cells, there were also dramatically lower levels of antigen-specific IgG. These age-related defects were not due to defects in migration of the aged CD4 T cells, but may be attributable to reduced CD154 (CD40L) expression. Furthermore, we found that there was no difference in B cell expansion and differentiation or in IgG production when young CD4 T cells were transferred to young or aged hosts. Our results show that, in this model, age-related reductions in the cognate helper function of CD4 T cells contribute significantly to defects in humoral responses observed in aged individuals. The Rockefeller University Press 2004-12-20 /pmc/articles/PMC2211991/ /pubmed/15611289 http://dx.doi.org/10.1084/jem.20041395 Text en Copyright © 2004, 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
Eaton, Sheri M.
Burns, Eve M.
Kusser, Kimberly
Randall, Troy D.
Haynes, Laura
Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses
title Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses
title_full Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses
title_fullStr Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses
title_full_unstemmed Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses
title_short Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses
title_sort age-related defects in cd4 t cell cognate helper function lead to reductions in humoral responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211991/
https://www.ncbi.nlm.nih.gov/pubmed/15611289
http://dx.doi.org/10.1084/jem.20041395
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