Functional properties of CD4+ CD28- T cells in the aging immune system

Cornelia M. Weyand, Johann Christoph Brandes, Dorle Schmidt, James W. Fulbright, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

143 Scopus citations

Abstract

The aging immune system is characterized by a progressive decline in the responsiveness to exogenous antigens and tumors in combination with a paradoxical increase in autoimmunity. From a clinical viewpoint, deficiencies in antibody responses to exogenous antigens, such as vaccines, have a major impact and may reflect intrinsic B cell defects or altered performance of helper T cells. Here we describe that aging is associated with the emergence of an unusual CD4 T cell subset characterized by the loss of CD28 expression. CD28 is the major costimulatory molecule required to complement signaling through the antigen receptor for complete T cell activation. CD4+ CD28- T cells are long-lived, typically undergo clonal expansion in vivo, and react to autoantigens in vitro. Despite the deficiency of CD28, these unusual T cells remain functionally active and produce high concentrations of interferon-γ (IFN-γ) and interleukin-2 (IL-2). The loss of CD28 expression is correlated with a lack of CD40 ligand expression rendering these CD4 T cells incapable of promoting B cell differentiation and immunoglobulin secretion. Aging-related accumulation of CD4+ CD28- T cells should result in an immune compartment skewed towards autoreactive responses and away from the generation of high-affinity B cell responses against exogenous antigens. We propose that the emergence of CD28-deficient CD4 T cells in the elderly can partially explain age-specific aberrations in immune responsiveness.

Original languageEnglish (US)
Pages (from-to)131-147
Number of pages17
JournalMechanisms of Ageing and Development
Volume102
Issue number2-3
DOIs
StatePublished - May 15 1998

Keywords

  • CD28
  • CD40 ligand
  • Cytokines
  • Helper cell function
  • Immunosenescense
  • T cells

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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