EVIDENCE THAT INDUCTION OF TOLERANCE IN-VIVO INVOLVES ACTIVE SIGNALING VIA A B7 LIGAND-DEPENDENT MECHANISM - CTLA4-IG PROTECTS V-BETA-8-CELLS FROM TOLERANCE INDUCTION BY THE SUPERANTIGEN STAPHYLOCOCCAL-ENTEROTOXIN-B( T)

Co-stimulation through CD28 is thought to be necessary for the activat ion of unprimed CD4(-) T cells, which are otherwise rendered tolerant. However, we previously found that CD4(-) T cell priming was normal or augmented in mice which overexpressed a soluble form of CTLA4 where c o-stimulation through CD28 was abrogated. To investigate this CD4(-) T cell response, we exploited the capacity of the superantigen staphylo coccal enterotoxin B to stimulate T lymphocytes bearing V beta 8(+), w hich represent similar to 30% of all CD4(+) T cells. In litter-mate co ntrols of CTLA4-Ig transgenic mice, immunization with staphylococcal e nterotoxin B leads to expansion, followed by deletion of V beta 8(+) T cells, and the remaining cells are tolerant when stimulated in vitro. Comparable expansion and deletion of V beta 8(+) T cells occurs in CT LA4-Ig transgenic mice. However, in contrast to normal mice, the remai ning V beta 8(+) T cells from CTLA4-Ig transgenic mice are not anergic and remain responsive to superantigen in vitro.