Prevention of superantigen-induced tolerance in vivo by interleukin-2 treatment

Injection of the superantigen staphylococcal enterotoxin A (SEA) activates both CD4(+) and CD8(+) T cells expressing certain families of T cell receptor (TCR) variable-region beta (V-beta) chain. T cells respond with profound cytokine production and induction of cytotoxicity. Repeated injections, however, cause deletion and anergy of both CD4(+) and CD8(+) T cells, resulting in reduced frequency of SEA-responsive cells TCR-V(beta)11(+) as well as reduced cytokine levels in serum upon challenge with SEA. Exogenous interleukin-2 (IL-2) in vivo rescued SEA-responsive CD4(+) and CD8(+) cells from SEA-induced deletion and/or increase expansion of SEA-primed cells as well as preventing downregulation of endogenous IL-2 production in vivo. Combined treatment with SEA and IL-2 also superinduced production of important cytokines for the cytotoxic function of T cells, tumour necrosis factor alpha, interferon gamma and IL-6, on a cellular level. These studies show that continuous stimulation with IL-2 in vivo could be useful for superantigen-based immunotherapy by induction of excessive T cell activation and by prevention of the development of T cell deletion and anergy.