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

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) Vβ8 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 Vβ8 gene family. In accord with these in vivo observations, IL‐2 is incapable of reversing “anergy” and apoptotic cell death of Vβ8+ SEB‐reactive T cells isolated from SEB‐primed mice in vitro. Accordingly, upon SEB injection Vβ8+ 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 Vβ8+ 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.