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.
Article|
July 01 1995
Prevention of age-related T cell apoptosis defect in CD2-fas-transgenic mice.
T Zhou,
T Zhou
Veterans Administration Medical Center, Birmingham, Alabama, USA.
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C K Edwards, 3rd,
C K Edwards, 3rd
Veterans Administration Medical Center, Birmingham, Alabama, USA.
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J D Mountz
J D Mountz
Veterans Administration Medical Center, Birmingham, Alabama, USA.
Search for other works by this author on:
T Zhou
Veterans Administration Medical Center, Birmingham, Alabama, USA.
C K Edwards, 3rd
Veterans Administration Medical Center, Birmingham, Alabama, USA.
J D Mountz
Veterans Administration Medical Center, Birmingham, Alabama, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1995) 182 (1): 129–137.
Citation
T Zhou, C K Edwards, J D Mountz; Prevention of age-related T cell apoptosis defect in CD2-fas-transgenic mice.. J Exp Med 1 July 1995; 182 (1): 129–137. doi: https://doi.org/10.1084/jem.182.1.129
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