Activation through CD40 ligation induces functional Fas ligand expression by Langerhans cells

Langerhans cells (LC) are professional antigen-presenting cells of dendriti c cell (DC) lineage and are critical for the induction of primary immune re sponses in skin. Following antigenic stimulation, LC migrate to regional ly mph nodes and induce antigen-specific activation of T cells. After primary expansion, the majority of T cells undergo Fas/Fas ligand (FasL)mediated ap optotic cell death, thereby suppressing their excessive expansion. Although recent investigations have indicated an immunoregulatory function for DC, whether LC could be involved in Fas/FasL-mediated suppression of activated T cells is still unclear. In this study, we found that LC express FasL afte r activation triggered through CD40 molecules on their surface, but not by stimulation with LPS or IFN-gamma. The functional significance of FasL expr ession by LC was demonstrated using two different assays for apoptosis indu ced in Jurkat cells. The apoptosis in Jurkat cells was completely blocked b y anti-FasL blocking antibody, suggesting a Fas/FasL-mediated mechanism. Th ese results indicate a new feedback mechanism to down-regulate T cell activ ation by LC through the interaction of the TNF receptor/ligand superfamily, CD40/CD40L and Fas/FasL.