Activated CD8(+) T cells from aged mice exhibit decreased activation-induced cell death.
To uncouple the defects of activation and apoptosis of T cells from aged mice, we used anti-CD3 plus IL-2 stimulation to induce an activation response and analyzed the subsequent activation-induced cell death (AICD) response of T cells from 16-month-old mice. The results herein demonstrate that T cells from 16-month-old mice could be activated by anti-CD3-induced activation signals but exhibited distinct phenotypic and functional features compared to young (2-month-old) mice. These include a decrease in AICD, a delayed entry into the cell cycle, and a decreased telomerase activity. The decreased AICD of T cells from 16-month-old mice is associated with a decreased expression of Fas and Fas ligand (FasL), decreased susceptibility to anti-Fas-induced apoptosis, and an increased expansion of a CD8(+) T-cell population. Prior to activation, these T cells exhibit a phenotype that is CD44(hi)CD62L(hi). After stimulation, these T cells produced high levels of the pro-inflammatory cytokine, IFN-gamma, and developed an increased population of IFN-gamma(+)IFN-gamma R(-) T cells. Our results suggest that there is a dysregulation in T-cell homeostasis in aged mice associated with a decrease in AICD of CD8(+) T cells.
Hsu
H C
HC
Division of Clinical Immunology and Rheumatology, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Shi
J
J
Yang
P
P
Xu
X
X
Dodd
C
C
Matsuki
Y
Y
Zhang
H G
HG
Mountz
J D
JD
D000375:Aging / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D015415:Biomarkers; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002453:Cell Cycle; D018960:Hyaluronan Receptors / Q000276:immunology; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D019041:L-Selectin; D008213:Lymphocyte Activation / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D019098:Telomerase / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D017252:CD3 Complex; D018960:Hyaluronan Receptors; D019041:L-Selectin; D007371:Interferon-gamma; D019098:Telomerase