Induction of unresponsiveness and impaired T cell expansion by Staphylococcal enterotoxin B in CD28-deficient mice

Abstract

We used CD28-deficient mice to analyze the importance of CD28 costimulation for the response against Staphylococcal enterotoxin B (SEB) in vivo. CD28 was necessary for the strong expansion of Vβ8+ T cells, but not for deletion. The lack of expansion was not due to a failure of SEB to activate Vβ8+ T cells, as Vβ8+ T cells from both CD28(-/-) and CD28(+/+) mice showed similar phenotypic changes within the first 24 h after SEB rejection and cell cycle analysis showed that an equal percentage of Vβ8+ T cells started to proliferate. However, the phenotype and the state of proliferation of Vβ8+ T cells was different at later time points. Furthermore, in CD28(-/-) mice rejection with SEB led to rapid reduction of unresponsiveness in SEB responsive T cells, indicated by a drastic reduction of proliferation after secondary SEB stimulation in vitro. Unresponsiveness could also be demonstrated in vivo, as CD28(-/-) mice produced only marginal amounts of TNFα after rechallenge with SEB. In addition CD28(-/-) mice were protected against a lethal toxic shock induced by a second injection with SEB. Our results indicate that CD28 costimulation is crucial for the T cell- mediated toxicity of SEB and demonstrate that T cell stimulation in the absence of CD28 costimulation induces unresponsiveness in vivo.