An age-related decrease in rescue from T cell death following costimulation mediated by CD28.

Abstract:

:We previously reported that T cell proliferation in response to a primary signal through the T cell receptor (TCR) and a costimulatory signal via the CD28 molecule is impaired in healthy, aged mice. Here we extend these studies to examine factors which may be involved in this defect in T cells from aged mice. To determine if age-related changes in cytokine production might be responsible, splenic T cells from young (2-4 months) and aged (20-26 months) mice were stimulated with immobilized anti-CD3 epsilon and soluble anti-CD28 mAbs in the presence of exogenous IL-2, IL-4, IFN-gamma, IL-1 alpha, or IL-6. No improvement in the proliferative response of T cells from aged mice was found following the addition of any cytokine. In addition, the decreased proliferative response of T cells from aged mice was not caused by the enhanced production of IFN-gamma or other inhibitory factors. Interestingly, despite the age-related reduction in proliferation, no significant difference was found in the percentage of live cells entering the S, G2, or AM phase of the cell cycle in stimulated T cells from young and aged mice. Instead, anti-CD28-mediated costimulation was found to rescue T cells from young mice from anti-CD3epsilon-induced cell death, but did not rescue T cells from aged mice. This failure of T cells from aged mice to respond to costimulatory signals appears to contribute to the decreased proliferation observed from cultures containing these cells, and may be involved in many other age-related alterations in immunological responsiveness.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Engwerda CR,Handwerger BS,Fox BS

doi

10.1006/cimm.1996.0144

subject

Has Abstract

pub_date

1996-05-25 00:00:00

pages

141-8

issue

1

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(96)90144-6

journal_volume

170

pub_type

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