DIFFERENTIAL ROLE OF TYROSINE PHOSPHORYLATION IN THE INDUCTION OF APOPTOSIS IN T-CELL CLONES VIA CD95 OR THE TCR CD3-COMPLEX/

Activated T cells undergo apoptosis when the Fas-antigen (APO-1, CD95) is ligated by Fas Ligand (FasL) or agonistic anti-Fas antibodies. Rep eated stimulation of T lymphocytes via the TCR/CD3-complex induces act ivation-induced cell death (AICD) associated with FasL surface express ion. FasL binding to Fas molecules triggers the Fas-dependent death si gnaling cascade. Since it is still controversial whether Fas-induced c ell death is associated with tyrosine kinase activity, we investigated the tyrosine kinase activation requirements in anti-Fas antibody-indu ced cell death and AICD in human T cell clones. We report that cell de ath triggered by anti-Fas antibody is not accompanied by an increase i n tyrosine phosphorylation and cannot be blocked by inhibitors of prot ein tyrosine kinases (PTK). Under the same conditions, AICD of T cell clones is clearly associated with tyrosine kinase activation. In fact, semiquantitative RT-PCR analysis of FasL mRNA expression triggered in T cell clones via the TCR/CD3-complex revealed that tyrosine phosphor ylation is required for functional FasL mRNA and surface expression.