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

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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.