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

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, G(2), or M 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-CD3 epsilon-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 de creased proliferation observed from cultures containing these cells, and may be involved in many other age-related alterations in immunological responsiveness. (C) 1996 Academic Press, Inc.