Age-related defects in CD4 T cell cognate helper function lead to reductions in humoral responses

J Exp Med. 2004 Dec 20;200(12):1613-22. doi: 10.1084/jem.20041395.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / immunology*
  • Aging / pathology
  • Animals
  • Antibody Formation* / genetics
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / transplantation
  • Cell Differentiation / immunology
  • Cell Movement / immunology
  • Gene Expression Regulation / immunology*
  • Germinal Center / immunology*
  • Germinal Center / pathology
  • Immunoglobulin G / immunology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Nitrophenols / administration & dosage
  • Nitrophenols / immunology
  • Phenylacetates / administration & dosage
  • Phenylacetates / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*

Substances

  • Antigens, CD
  • Immunoglobulin G
  • Nitrophenols
  • Phenylacetates
  • Receptors, Antigen, T-Cell
  • 4-hydroxy-5-nitrophenyl acetic acid