Anti-Fas antibody-induced maturation of dendritic cells is mediated through Fcγ receptor

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Objective : It has been reported that dendritic cells (DCs) are not susceptible to Fas-mediated cell death and that the engagement of Fas on DCs rather induces their phenotypical maturation. In this report we tried to reproduce such observations and to analyze the underlying mechanism of transduction of the putative Fas-mediated maturation signal. Results : Treatment of bone marrow-derived DCs with anti-Fas antibody (Jo2) indeed promoted maturation of DCs, as characterized by the enhanced expression of class II MHC antigens and CD86. However, this effect turned out not to be specific to anti-Fas antibody. Instead, antibodies to class I MHC antigen and FcγR also exerted a similar effect, suggesting the involvement of FcγR. When DCs of FcR-γ chain (-/-) mice, lacking the expression of FcγR I and III, were treated with Jo2, facilitation of maturation was not observed confirming the involvement of FcγR in transduction of the maturation signal. When DCs of normal mice were treated with soluble Fas ligand (FasL), only apoptosis was induced among DCs. Immature DCs were more sensitive to the apoptosis induction thus resulting in apparent increase in the percentage of mature DCs. Nevertheless, there was absolutely no evidence for facilitation of maturation by FasL. Conclusions : All and all, these results cast serious doubts about the validity of the observations concerning putative maturation signal transduction by Fas molecules.
2004-03-31