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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...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2004
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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. |
format | Text |
id | pubmed-2211991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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