The role of IL-4 in the staphylococcal enterotoxin B-triggered immune response: increased susceptibility to shock and deletion of CD8V beta(+) T cells in IL-4 knockout mice

Abstract

Administration of superantigens in vivo triggers responding T cells into clonal expansion and subsequent activation of the programmed cell death pathway, as well as into anergy. We examined the possibility that Th1 cytokines are involved in rescue from superantigen-induced programmed cell death and prevention of anergy by studying the Staphylococcus aureus enterotoxin B (SEB) immune response in mice in which the IL-4 gene was deleted (IL-4(-/-)). In these mice, Th1 cell activation triggers increased IFN-gamma, and reduced IL-5 production as compared to IL-4(+/+) mice. The primary anti-SEE antibody response in IL-4(-/-) mice is thus dominated by immunoglobulins of the IgG2a isotype, whereas the IgG1 isotype prevails in IL-4(+/+) mice. Our results also show that, in contrast to expectations, IL4(-/-) mice are more susceptible to SEE plus low-dose o-galactosamine-induced shock and that this response is TNF-alpha-dependent. In vivo treatment induces partial deletion and anergy of remaining SEB-reactive T cells. During the SEB-induced response, CD4V beta 8(+) T cells are deleted in IL-4(-/-) mice, but not in IL-4(+/+) mice, suggesting a function for IL-4 in CD8(+) T cell rescue from apoptosis. We show that IL-4 efficiently protects CD8(+) T cells from in vitro starvation-induced apoptosis, and conclude that IL-4 has an important role in Th1 immune response regulation.