title: Differential role of tyrosine phosphorylation in the induction of apoptosis in T cell clones via CD95 or the TCR/CD3-complex.
abstract: Activated T cells undergo apoptosis when the Fas-antigen (APO-1, CD95) is ligated by Fas Ligand (FasL) or agonistic anti-Fas antibodies. Repeated stimulation of T lymphocytes via the TCR/CD3-complex induces activation-induced cell death (AICD) associated with FasL surface expression. FasL binding to Fas molecules triggers the Fas-dependent death signaling cascade. Since it is still controversial whether Fas-induced cell death is associated with tyrosine kinase activity, we investigated the tyrosine kinase activation requirements in anti-Fas antibody-induced cell death and AICD in human T cell clones. We report that cell death triggered by anti-Fas antibody is not accompanied by an increase in tyrosine phosphorylation and cannot be blocked by inhibitors of protein 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 phosphorylation is required for functional FasL mRNA and surface expression.
authors.affiliation: Department of Immunology, Paul-Ehrlich-Institute, D63225 Langen, Germany.
authors.forename: H H
authors.initials: HH
authors.lastname: Oberg
authors.forename: B
authors.initials: B
authors.lastname: Lengl-Janssen
authors.forename: M J
authors.initials: MJ
authors.lastname: Robertson
authors.forename: D
authors.initials: D
authors.lastname: Kabelitz
authors.forename: O
authors.initials: O
authors.lastname: Janssen