Nuclear factor of activated T cells transcription factor NFATp controls superantigen-induced lethal shock

Turner necrosis factor alpha (TNF-alpha) is the key mediator of superantige n-induced T cell lethal shock. Here, we show that nuclear factor of activat ed T cells transcription factor, NFATp, controls susceptibility to superant igen-induced lethal shock in mice through its activation of TNF-alpha gene transcription. In NFATp-deficient mice, T cell stimulation leads to delayed induction and attenuation of TNF-alpha mRNA levels, decreased TNF-alpha se rum levels, and resistance to superantigen-induced lethal shock. By contras t, after lipopolysaccharide (LPS) challenge, serum levels of TNF-alpha and susceptibility to shock are unaffected. These results demonstrate that NFAT p is an essential activator of immediate early TNF-alpha gene expression in T cells and they present in vivo evidence of the inducer- and cell type-sp ecific regulation of TNF-alpha gene expression. Furthermore, they suggest N FATp as a potential selective target in the treatment of superantigen-induc ed lethal shock.