Prevention of age-related T cell apoptosis defect in CD2-fas-transgenic mice

Academic Article

Abstract

  • T cell dysfunction and thymic involution are major immunologic abnormalities associated with aging. Fas (CD95) is a bifunctional molecule that is critical for apoptosis and stimulation during T cell development, but the role of Fas during aging has not been determined. Fas expression and function on T cells from old (22-26-mo-old) mice was compared with young (2-mo-old) mice and old CD2-Jhs-transgenic mice. Fas expression and ligand-induced apoptosis were decreased on T cells from old mice compared with young mice. This correlated with an age-related increase in CD44+Fas− T cells. There was a marked decrease in the proliferation of T cells from old mice after anti-CD3 stimulation compared with young mice. Anti-CD3-stimulated T cells from young mice exhibited increased production of interleukin (IL)-2 and decreased production of interferon-γ and IL-10 compared with old mice. There was an age-related decrease in the total thymocyte count from 127 ± 10 cells in young mice compared with 26 ± 8 × 106 in old mice. In 26-mo-old CD2-fas-transgenic mice, Fas and CD44 expression, Fas-induced apoptosis, T cell proliferation, and cytokine production were comparable to that of the young mice. These results suggest that T cell senescence with age is associated with defective apoptosis, and that the CD2-fhs transgene allows maintenance of Fas apoptosis function and T cell function in aged mice comparable to that of young mice. © 1995, Rockefeller University Press., All rights reserved.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Zhou T; Edwards CK; Mountz JD
  • Start Page

  • 129
  • End Page

  • 137
  • Volume

  • 182
  • Issue

  • 1