Transferable Anergy: Superantigen Treatment Induces CD4⁺ T Cell Tolerance That Is Reversible and Requires CD4⁻CD8⁻ Cells and Interferon γ

Bacterial superantigens induce peripheral unresponsiveness in CD4⁺ T cell populations that express appropriate Vβ chains. We have used Vβ3/Vα11 T cell receptor transgenic (Tg) mice and the Vβ3-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⁺ cells unresponsive to subsequent restimulation in vitro with antigen or mitogens. However, when the SEA-treated CD4⁺ cells were completely purified away from all other contaminating cells, they regained the ability to proliferate and secrete cytokines. Moreover, enriched CD4⁻CD8⁻ cells from the SEA-treated mice suppressed the responses of fresh control CD4⁺ cells in mixed cultures indicating that the apparent “anergy” was both transferable and reversible. Further analysis demonstrated that interferon γ, but not the Fas receptor, played a critical role in the suppression.