Prevention of age-related T cell apoptosis defect in CD2-fas-transgenic mice.
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-fas-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-gamma 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 x 10(6) 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-fas transgene allows maintenance of Fas apoptosis function and T cell function in aged mice comparable to that of young mice.
Zhou
T
T
Veterans Administration Medical Center, Birmingham, Alabama, USA.
Edwards
C K
CK
Mountz
J D
JD
D000375:Aging / Q000276:immunology*; D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000235:genetics*; D018801:CD2 Antigens / Q000096:biosynthesis / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018960:Hyaluronan Receptors; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000276:immunology; D019014:fas Receptor
D000954:Antigens, Surface; D018801:CD2 Antigens; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D011956:Receptors, Cell Surface; D016201:Receptors, Lymphocyte Homing; D011993:Recombinant Fusion Proteins; D019014:fas Receptor