Activation-induced apoptosis in T cells from young and old Fischer 344 rats

Background: Activation-induced apoptosis is believed to limit cell prolifer ation and eliminate the high number of activated cells during an immune res ponse. Methods: Activation-induced apoptosis was investigated in splenic T cells isolated from young (6 months) and old (24 months) male Fischer 344 r ats. The cells were incubated with anti-CD3, concanavalin A or staphylococc al enterotoxin B (primary stimulus) for 72 h, followed by restimulation wit h anti-CDB or concanavalin A (secondary stimulus). Apoptosis was assessed b y DNA fragmentation assay and DNA gel electrophoresis. The expression of th e apoptotic marker CD95 was analyzed by flow cytometry and the relative lev els of CD95 ligand, Bcl-2 and Bar protein were measured by immunoblotting. Results: It was shown that DNA fragmentation was very low in the unstimulat ed T cells from both young and old rats. However, the level of DNA fragment ation was 45-55% great er in the activated T cells from old rats than in th e activated T cells from young rats. The increase in DNA fragmentation was paralleled by an increase in the proportion of cells expressing the CD95 mo lecule. The proportion of CD95+ cells was approximately 40% higher in T cel ls from old rats than in T cells from young rats. In addition, it was found that the expression of CD95 ligand and Bar increased and Bcl-2 decreased i n the activated T cells from old rats compared to the activated T cells fro m young rats, Conclusion: Our data suggest that the increase in sensitivity of T cells to apoptosis with age may contribute to age-associated immune d ysfunction and disorders. Copyright (C) 2000 S. Karger AG, Basel.