The Journal of Experimental Medicine
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J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/07/71/11 $2.00
Volume 186, Number 1, July 7, 1997 71-81

Transferable Anergy: Superantigen Treatment Induces CD4+ T Cell Tolerance That Is Reversible and Requires CD4minus CD8minus Cells and Interferon gamma

By Linda S. Cauley,* Keith A. Cauley,* Fillipa Shub,Dagger Gail Huston,* and Susan L. Swain*

From the * Trudeau Institute, Saranac Lake, New York 12983; and Dagger  Cancer Center, University of California at San Diego, La Jolla, California 92093

Bacterial superantigens induce peripheral unresponsiveness in CD4+ T cell populations that express appropriate Vbeta chains. We have used Vbeta 3/Valpha 11 T cell receptor transgenic (Tg) mice and the Vbeta 3-specific superantigen staphylococcal enterotoxin A (SEA) to further investigate the mechanisms that contribute to such unresponsiveness. As in other models, in vivo exposure to SEA rendered the Tg CD4+ cells unresponsive to subsequent restimulation in vitro with antigen or mitogens. However, when the SEA-treated CD4+ cells were completely purified away from all other contaminating cells, they regained the ability to proliferate and secrete cytokines. Moreover, enriched CD4-CD8- cells from the SEA-treated mice suppressed the responses of fresh control CD4+ cells in mixed cultures indicating that the apparent "anergy" was both transferable and reversible. Further analysis demonstrated that interferon gamma , but not the Fas receptor, played a critical role in the suppression.


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