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) V beta 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 beta 8 gene family. In accord with these in vivo observations, IL-2 is incapable of reversing "anergy" and apoptotic cell death of V beta 8+ SEB-reactive T cells isolated from SEB-primed mice in vitro. Accordingly, upon SEB injection V beta 8+ T cells expand rapidly, without expressing IL-2 receptor (IL-2R)alpha chains in vivo, although SEB induces IL-2R alpha 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 beta 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.
Gonzalo
J A
JA
Centro de Biología Molecular, CSIC, Universidad Autónoma, Madrid, Spain.
Moreno de Alborán
I
I
Alés-Martínez
J E
JE
Martínez
C
C
Kroemer
G
G
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division; D016572:Cyclosporine / Q000494:pharmacology; D004768:Enterotoxins / Q000276:immunology*; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000942:Antigens, Bacterial; D004768:Enterotoxins; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; C031818:enterotoxin B, staphylococcal; D016572:Cyclosporine