ACTIVATION-INDUCED EXPRESSION OF THYMIC SHARED ANTIGEN-1 ON T-LYMPHOCYTES AND ITS INHIBITORY POLE FOR TCR-MEDIATED IL-2 PRODUCTION

We have produced a hamster mAb, PRST1, which reacts with thymic shared Ag-1 (TSA-1), a product of the Ly6 gene family. By cross-blocking exp eriments, we found that TSA-1 is identical to stem cell Ag-2 (Sca-2). Using PRST1, the changes of TSA-1/Sca-2 expression on mature T cells d uring the activation process were analyzed. Although freshly isolated T cells did not express detectable TSA-1 on their cell surface, in vit ro stimulation of T cells with concanavalin A induced a marked increas e of surface TSA-1 expression. The increased expression of TSA-1 on T cells was detected from 12 h after stimulation and was associated with the increase of TSA-1 mRNA. In vivo injection of mice with staphyloco ccal enterotoxin B (SEB) resulted in the enhanced TSA-1 expression in splenic V(beta)8(+) T cells. This antigen-specific induction of TSA-1 expression in vivo preceded a detectable increase in numbers of V(beta )8(+) T cells after SEB injection. Functionally, whereas anti-TSA-1 mA b was not mitogenic to T cells, it inhibited anti-CD3-induced IL-2 pro duction by T cell hybridomas. These results indicate that TSA-1/Sca-2 is a unique marker for T cell activation and a signal through this mol ecule may have a negative feedback role to limit IL-2 production from activated T cells stimulated through the TCR.