Evidence that induction of tolerance in vivo involves active signaling via a B7 ligand‐dependent mechanism: CTLA4‐Ig protects Vβ8+ T cells from tolerance induction by the superantigen staphylococcal enterotoxin B

Abstract

Co-stimulation through CD28 is thought to be necessary for the activation 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 co-stimulation through CD28 was abrogated. To investigate this CD4⁺ T cell response, we exploited the capacity of the superantigen staphylococcal enterotoxin B to stimulate T lymphocytes bearing Vβ8⁺, which represent ϰ30% of all CD4⁺ T cells. In littermate controls of CTLA4-Ig transgenic mice, immunization with staphylococcal enterotoxin B leads to expansion, followed by deletion of Vβ8⁺ T cells, and the remaining cells are tolerant when stimulated in vitro. Comparable expansion and deletion of Vβ8⁺ T cells occurs in CTLA4-Ig transgenic mice. However, in contrast to normal mice, the remaining Vβ8⁺ T cells from CTLA4-Ig transgenic mice are not anergic and remain responsive to superantigen in vitro.