Transferable Anergy : Superantigen Treatment Induces CD 4 1 T Cell Tolerance That Is Reversible and Requires CD 4 2 CD 8 2 Cells and Interferon

Bacterial superantigens induce peripheral unresponsiveness in CD4 1 T cell populations that express appropriate V b chains. We have used V b 3/V a 11 T cell receptor transgenic (Tg) mice and the V b 3-specific superantigen staphylococcal enterotoxin A (SEA) to further investigate the mechanisms that contribute to such unresponsiveness. As in other models, in vivo exposure to SEA rendered the Tg CD4 1 cells unresponsive to subsequent restimulation in vitro with antigen or mitogens. However, when the SEA-treated CD4 1 cells were completely purified away from all other contaminating cells, they regained the ability to proliferate and secrete cytokines. Moreover, enriched CD4 2 CD8 2 cells from the SEA-treated mice suppressed the responses of fresh control CD4 1 cells in mixed cultures indicating that the apparent “anergy” was both transferable and reversible. Further analysis demonstrated that interferon g , but not the Fas receptor, played a critical role in the suppression.