In vivo induction of anergy in peripheral Vβ8+ T cells by staphylococcal enterotoxin B

Abstract

We have developed a model of peripheral in vivo T cell tolerance that is induced by administration of the protein superantigen staphylococcal enterotoxin B (SEB). Rather than activating VβS+ T cells, in vivo administration of SEB induced in them a profound state of anergy. This was shown by their failure to proliferate to subsequent in vitro restimulation with SEB or to anti-Vβ8 antibodies. This unresponsiveness was Vβ8 specific since T cells from SEB-immunized mice responded normally to other antigens. 8 d after SEB administration, there was no reduction in the number of Vβ8+ T cells or in the intensity of Vβ8 T cell receptor (TCR) expression. Although a portion of the Vβ8+ T cells from SEB-primed mice were able to express interleukin 2 receptors (IL-2Rs), they failed to proliferate in response to exogenous IL-2, indicating they were defective in their IL-2 responsiveness. 2-4 wk after SEB administration, there was a reduction of ∼50% in the number of Vβ8+ cells in immunized compared with control animals. There was, however, no reduction in the level of TCR expression on the remaining Vβ8+ cells. These data demonstrate that proteins that activate T cells in vitro in a Vβ-specific manner can induce a state of anergy in peripheral T cells in vivo and may possibly further mediate clonal deletion in a portion of the tolerized cells.