ANTIGEN PRESENTATION BY ASTROCYTES PRIMES RAT T-LYMPHOCYTES FOR APOPTOTIC CELL-DEATH - A MODEL FOR T-CELL APOPTOSIS IN-VIVO

In this study we have characterized apoptotic cell death of autoreacti ve T cells resulting from their interaction with astrocytes and the mo dulatory effect of steroid hormones. Time kinetics of T-cell activatio n by interferon (IFN)-gamma-treated astrocytes from neonatal Lewis vat s and by professional antigen presenting cells (APCs) from bulk suspen sions of thymus or spleen were performed [H-3]Thymidine incorporation of neuritogenic P-2- and encephalitogenic myelin basic protein (MBP)-s pecific T-cell fines declined after 48 h in culture with astrocytes. A similar suppressive effect was observed when T cells were cocultured with thymic APCs and astrocytes. This effect disappeared when astrocyt es were separated by a transwell system. After 72 h of culture with as trocytes a mean of 17.5 +/- 12.4% T cells exhibited morphological sign s of apoptosis. Apoptosis was identified by Eight microscopy, and conf irmed by electron microscopy, by in situ tailing reaction and by agaro se gel electrophoresis. Glucocorticosteroids and oestrogen specificall y enhanced T-cell apoptosis within 8 h (69.8 +/- 23.1% and 69 +/- 17.1 %, respectively) when added after 72 h to the astrocyte system, but no t at earlier time points of T-cell activation or when thymic APCs were used. Glucocorticoid-mediated T-cell apoptosis was inhibited by the s teroid-receptor antagonist RU 486. Pregnenolone, lipocortin-1, indomet hacin and transforming growth factor-beta did not induce apoptosis in this system. The steroid effect was not associated with CD28, IL-2 rec eptor or transferrin-receptor expression, which were equally upregulat ed on T cells activated by astrocytes or thymic APC as shown by fluore scence activated cell sorting (FACS) analysis. We conclude that astroc ytes as CNS-specific APC may render T cells susceptible for induction of apoptotic cell death. Some steroid hormones can markedly enhance th is process in vitro and may augment art additional effect of a systemi c corticosteroid response in vivo during recovery from autoimmune ence phalomyelitis.