Nuclear Factor of Activated T Cells Transcription Factor NFATp Controls Superantigen-induced Lethal Shock

doi:10.1084/jem.192.4.581

Published online 21 August 2000.

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© The Rockefeller University Press, 0022-1007/2000/8/581/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 4, August 21, 2000 581-586

Brief Definitive Report

Nuclear Factor of Activated T Cells Transcription Factor NFATp Controls Superantigen-induced Lethal Shock

Alla V. Tsytsykova^a and Anne E. Goldfeld^a
^a From The Center for Blood Research and Harvard Medical School and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

Correspondence to: Anne E. Goldfeld, The Center for Blood Research and Harvard Medical School, 800 Huntington Ave., Boston, MA 02115. Tel:617-278-3351 Fax:617-278-3454 E-mail:goldfeld{at}cbr.med.harvard.edu.

Tumor necrosis factor ${alpha}$ (TNF- ${alpha}$ ) is the key mediator of superantigen-inducedT cell lethal shock. Here, we show that nuclear factor of activatedT cells transcription factor, NFATp, controls susceptibilityto superantigen-induced lethal shock in mice through its activationof TNF- ${alpha}$ gene transcription. In NFATp-deficient mice, T cellstimulation leads to delayed induction and attenuation of TNF- ${alpha}$ mRNA levels, decreased TNF- ${alpha}$ serum levels, and resistance tosuperantigen-induced lethal shock. By contrast, after lipopolysaccharide(LPS) challenge, serum levels of TNF- ${alpha}$ and susceptibility toshock are unaffected. These results demonstrate that NFATp isan essential activator of immediate early TNF- ${alpha}$ gene expressionin T cells and they present in vivo evidence of the inducer-and cell type–specific regulation of TNF- ${alpha}$ gene expression.Furthermore, they suggest NFATp as a potential selective targetin the treatment of superantigen-induced lethal shock.

Key Words: tumor necrosis factor ${alpha}$ , staphylococcal enterotoxin B, lipopolysaccharide,transcription, toxic shock

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