Av. Tsytsykova et Ae. Goldfeld, Nuclear factor of activated T cells transcription factor NFATp controls superantigen-induced lethal shock, J EXP MED, 192(4), 2000, pp. 581-586
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.