Lung fibroblasts inhibit activation-induced death of T cells through PGE(2)-dependent mechanisms

Activation-induced cell death (AICD) is a regulatory mechanism eliminating excess activated T cells, mainly through a Fas/Fas ligand-dependent mechani sm. The goal of this study was to determine whether mouse primary lung fibr oblasts are capable of modulating AICD. Using T cell hybridoma DO11.10, we found that fibroblasts in coculture rescue T cells from AICD. Fibroblast-co nditioned medium (FCM) also inhibited apoptosis of T cells activated with i mmobilized anti-CD3 antibody. The effects of lung fibroblasts are mediated, in part, by secreted prostaglandin E-2 (PGE(2)) because treatment of fibro blasts with indomethacin decreased antiapoptotic activity of FCM. Addition of exogenous PGE(2) to FCM from fibroblast cultures treated with indomethac in restored the inhibitory activity of FCM. Expression of Fas receptor and Fas ligand by anti-CD3-activated DO11.10 cells was not affected by PGE(2). However, the same concentrations of PGE(2) significantly downregulated acti vation of caspase-8 and caspase-3. These results demonstrate that lung fibr oblasts inhibit the AICD of T cells by secreting PGE(2), which downregulate s caspase activation and apoptosis.