The Uab Research Foundation

Changdan Liu

Tong Zhou

William J Koopman

John D Mountz

Jianhua Cheng

Disclosed is a 5' flanking sequence of the human fas gene containing a promoter region. This sequence also contains at least three transcription initiation sites, as well as consensus sequences for AP-1, GF-1, NY-Y, CP-2, EB20, and c-myb. Also disclosed are methods of altering senescence of the immune system by modifying Fas activity in cells to increase or decrease apoptosis. Fas expression and function on T cells from old (22-26-month-old) mice is also compared to young (2-month-old) mice and old CD2-fas transgenic mice. Fas expression and ligand-induced apoptosis was decreased on T cells from old mice compared to young mice. In 26-month-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 the maintenance of Fas apoptosis function and T cell function in aged mice comparable to that of young mice.

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Alabaster, AL, United States of America

Changdan Liu