PREVENTION OF SUPERANTIGEN-INDUCED TOLERANCE IN-VIVO BY INTERLEUKIN-2TREATMENT

Injection of the superantigen staphylococcal enterotoxin A (SEA) activ ates both CD4(+) and CD8(+) T cells expressing certain families of T c ell receptor (TCR) variable-region beta (V-beta) chain. T cells respon d with profound cytokine production and induction of cytotoxicity. Rep eated injections, however, cause deletion and anergy of both CD4(+) an d CD8(+) T cells, resulting in reduced frequency of SEA-responsive cel ls TCR-V(beta)11(+) as well as reduced cytokine levels in serum upon c hallenge with SEA. Exogenous interleukin-2 (IL-2) in vivo rescued SEA- responsive CD4(+) and CD8(+) cells from SEA-induced deletion and/or in crease expansion of SEA-primed cells as well as preventing downregulat ion 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, interfero n gamma and IL-6, on a cellular level. These studies show that continu ous stimulation with IL-2 in vivo could be useful for superantigen-bas ed immunotherapy by induction of excessive T cell activation and by pr evention of the development of T cell deletion and anergy.