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The Journal of Immunology, Vol 159, Issue 3 1135-1139, Copyright © 1997 by American Association of Immunologists

ARTICLES

ZAP-70 tyrosine kinase is required for the up-regulation of Fas ligand in activation-induced T cell apoptosis

CM Eischen, BL Williams, W Zhang, LE Samelson, DH Lynch, RT Abraham and PJ Leibson
Department of Immunology, Mayo Clinic and Foundation, Rochester, MN 55905-0001, USA.

Activation-induced cell death (AICD) is initiated by the TCR-dependent up-regulation of Fas ligand (FasL) mRNA. The subsequently generated soluble or cell-associated FasL gene products bind Fas, leading to apoptosis of the T cells. Although TCR stimulation is essential to initiate AICD, little is known about which TCR-initiated second messengers are required for FasL expression. We provide evidence in this work that T cells lacking the tyrosine kinase ZAP-70 are unable to up-regulate FasL and undergo AICD. Transfection of wild-type ZAP-70 into the ZAP-70-deficient T cells restores their sensitivity to TCR- induced apoptosis, whereas transfection of catalytically inactive ZAP- 70 does not. These results provide clear evidence that ZAP-70 tyrosine kinase is essential in up-regulating FasL for TCR-induced apoptosis.


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