CTLA-4 REGULATES TOLERANCE INDUCTION AND T-CELL DIFFERENTIATION IN-VIVO

Cytotoxic T lymphocyte Ag-4 (CTLA-4; CD152) is an important T cell reg ulatory molecule, In vitro experiments have shown that the blockade of signals through CTLA-4 augments T cell expansion, while CTLA-4 cross- linking results in decreased T cell proliferation due to decreased IL- 2 production, However, Less is known about the role of CTLA-4 in regul ating an ongoing immune response, In this study, we examined the role of CTLA-4 in the expansion, decline, tolerization, and differentiation of T cells following treatment with staphylococcal enterotoxin B (SEB ), Anti-CTLA-4 treatment resulted in increased numbers of SEB-reactive T cells and blockade of subsequent tolerance induction, Further exami nation of the SEE-reactive cells from anti-CTLA-4-treated mice demonst rated that both the CD4(+) and CD8(+) V(beta)8(+) T cells produced IL- 4, providing evidence that not only do signals through CTLA-4 regulate T cell-tolerizing events, but they also play an important role in the differentiation of T cells in vivo.