The molecular mechanism of FasL-mediated cytotoxicity by CD4+ Th1 clones

Cellular Immunology
M el-KhatibS T Ju

Abstract

Murine CD4+ Th1 clones require de novo synthesis of proteins to express a cytotoxicity that is mediated by de novo synthesized Fas ligand (FasL). The cytotoxic process of the CD4+ Th1 effectors can be separated into four stages, namely conjugate formation, activation, lethal hit, and effector-independent target cell death. The present study describes the cytotoxic process in terms of FasL induction and Fas/FasL molecular interactions for death signal transduction. Fas-Ig fusion proteins, cycloheximide, actinomycin D, and EGTA+MgCl2 were used to analyze each stage of the cytotoxic process in terms of FasL/Fas participation. The results demonstrate that the activation-induced de novo mRNA and protein synthesis were for FasL, which provided the predominant cytotoxic activity of CD4+ Th1 effectors. Once activated, Th1 effectors express cytotoxic activity in the presence of EGTA+MgCl2, an experimental [Ca2+]ext-independent condition characteristic of FasL-mediated cytotoxicity. The ability of Fas-Ig to inhibit target lysis declined rapidly after conjugate formation, indicating that FasL-mediated lethal hit is critically dependent on conjugate formation and, once delivered, the effector-independent target lysis proceeds. After the le...Continue Reading

Citations

Dec 1, 1996·The Journal of Experimental Medicine·S D D'SouzaJ P Antel
Jul 8, 1997·Proceedings of the National Academy of Sciences of the United States of America·H CuiS T Ju
Aug 14, 2013·The British Journal of Dermatology·B O Dulmage, L J Geskin
Oct 1, 1996·The Tohoku Journal of Experimental Medicine·M SatohT Toyota
Jul 14, 1999·Immunity·D A HildemanP C Marrack
May 9, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·S JodoS T Ju

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