Expansion and clonal deletion of peripheral T cells induced by bacterial superantigen is independent of the interleukin‐2 pathway

Abstract Injection of the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) into mice provokes a rapid expansion and subsequent contraction of the pool of SEB‐reactive T cells bearing T cell receptor (TcR) V β 8 gene products. Given that interleukin 2 (IL‐2) stimulates proliferation, abolishes anergy, and counteracts apoptotic cell death in T cells in vitro , we tested whether the IL‐2 synthesis inhibitor cyclosporin A (CsA) or a vaccinia virus recombinant releasing high amounts of human IL‐2 modulate SEB responses in vivo . Surprisingly, neither IL‐2 nor CsA were able to change the in vivo kinetics and magnitude of SEB‐induced expansion, unresponsiveness to SEB, and peripheral clonal deletion of T cells expressing products of the SEB‐reactive TcR V β 8 gene family. In accord with these in vivo observations, IL‐2 is incapable of reversing “anergy” and apoptotic cell death of V β 8 + SEB‐reactive T cells isolated from SEB‐primed mice in vitro . Accordingly, upon SEB injection V β 8 + T cells expand rapidly, without expressing IL‐2 receptor (IL‐2R)α chains in vivo , although SEB induces IL‐2R α in vitro . Altogether, these results indicate that the IL‐2/IL‐2R‐mediated pathway is not involved in T cell repertoire modulation by bacterial superantigens. Moreover, the data suggest that unresponsiveness of V β 8 + T cells from SEB‐primed mice is not a reversible process, but involves an unreversible commitment to programmed cell death. Absence or presence of IL‐2 responsiveness could be a hallmark to distinguish truly reversible anergy and peripheral clonal deletion.