{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:48:12Z","timestamp":1770720492834,"version":"3.49.0"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2005,11,23]],"date-time":"2005-11-23T00:00:00Z","timestamp":1132704000000},"content-version":"vor","delay-in-days":4071,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1994,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fas\/APO\u20101 is a member of the tumor necrosis factor receptor family of proteins, that induces apoptosis when cross\u2010linked with monoclonal antibody (mAb) or with its physiological ligand. Recently, both a perforin\u2010based and a Fas\u2010based mechanism have been proposed to account for T cell\u2010mediated cytotoxicity. In the present study we used a murine CD8<jats:sup>+<\/jats:sup> cytotoxic T lymphocyte (CTL) clone (KB5.C20) specific for H\u20102K<jats:sup>b<\/jats:sup> and a T cell receptor (TcR)\u2010negative variant of the same clone (2005<jats:sup>\u2212<\/jats:sup>D4) to test (i) whether the same cell can exert both cytotoxic effector mechanisms and (ii) the role of TcR engagement in the induction of Fas\u2010based cytotoxicity. We demonstrate that both the TcR<jats:sup>+<\/jats:sup> and TcR<jats:sup>\u2212<\/jats:sup> clones were able to express the Fas ligand after stimulation with phorbol 12\u2010myristate 13\u2010acetate (PMA)\/ionomycin, and that TcR engagement of the KB5.C20 clone by means of antigen\u2010bearing cells or of its anticlonotypic mAb (D\u00e9sir\u00e9\u20101), which leads to Ca<jats:sup>2+<\/jats:sup>\u2010dependent, presumably perforin\u2010based, cytotoxicity, was also able to induce Fas\u2010based cytotoxicity. In addition, using inhibitors we investigated the signal transduction pathway(s) involved in the induction of Fas\u2010based cytotoxicity and expression of the Fas ligand mRNA in the CTL clones. The involvement of <jats:italic>src<\/jats:italic>\u2010like protein tyrosine kinases (PTK) in Fas ligand induction through TcR engagement, was strongly suggested by inhibition with the <jats:italic>src<\/jats:italic>\u2010like PTK inhibitor herbimycin A. Inhibition of Fas ligand induction by genistein, a more general TPK inhibitor, even upon stimulation by PMA plus ionomycin, suggested the possible involvement of PTK activities downstream of protein kinase C (PKC) in Fas ligand induction in CTL. Finally, the implication of the Ca<jats:sup>2+<\/jats:sup>\/calmodulin\u2010dependent protein phosphatase calcineurin in Fas ligand induction was demonstrated by the partial inhibition of Fas ligand induction with cyclosporin A. Thus, in CTL clones, Fas ligand expression is inducible by TcR engagement through a pathway similar to that involved in expression of some lymphokine genes.<\/jats:p>","DOI":"10.1002\/eji.1830241032","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T19:59:55Z","timestamp":1172779195000},"page":"2469-2476","source":"Crossref","is-referenced-by-count":127,"title":["T cell receptor\u2010induced Fas ligand expression in cytotoxic T lymphocyte clones is blocked by protein tyrosine kinase inhibitors and cyclosporin A"],"prefix":"10.1002","volume":"24","author":[{"given":"Alberto","family":"Anel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Buferne","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claude","family":"Boyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Marie","family":"Schmitt\u2010Verhulst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Golstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,23]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.169.5.1747"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2787530"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/356314a0"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/6.1.73"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.10.4409"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830240421"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.1.195"},{"key":"e_1_2_1_9_2","unstructured":"Luciani M. 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