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, 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.
Engwerda
C R
CR
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland, Baltimore 21201, USA. c.engwerda@lshtm.ac.uk
Handwerger
B S
BS
Fox
B S
BS
D000375:Aging / Q000276:immunology*; D000818:Animals; D018106:CD28 Antigens / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology*; D006131:Growth Inhibitors / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D018106:CD28 Antigens; D006131:Growth Inhibitors; D007376:Interleukin-2; D015847:Interleukin-4