Dendritic cells undergo rapid apoptosis in vitro during antigen-specific interaction with CD4(+) T cells

The terminal fate of dendritic cells (DC) remains relatively uncertain. In this study, we tested the hypothesis that DC undergo apoptosis after Ag-spe cific interaction with T cells, When splenic DC isolated from BALB/c mice w ere cocultured with HDK-1 T cells (a keyhole limpet hemocyanin (KLH)-specif ic CD4(+) Th1 clone) in the presence of KLH, they showed conspicuous cell d eath as measured by propidium iodide (PI) uptake and chromatin condensation , whereas they remained relatively intact when incubated with either T cell s or KLH alone, Likewise, the long term DC line XS52, which was established from BALB/c mouse epidermis, also died rapidly (within 2 h), and they exhi bited characteristic DNA laddering when cocultured with HDK-1 T cells in th e presence of KLH. RT-PCR and FAGS analyses revealed the expression of CD95 (Fas) by XS52 DC and of CD95 Ligand (CD95L) (Fas ligand) by activated HDK- 1 T cells, suggesting a functional role for these molecules. Zn fact, anti- CD95L mAb inhibited partially (50%) T cell-mediated XS52 cell death, and co upling of surface CD95 with anti-CD95 mAb triggered significant XS52 cell d eath, but only in the presence of cycloheximide, Thus, ligation of CD95 (on DC) with CD95L (on T cells) is one, but not the only, mechanism by which T cells induce DC death. Finally, DC isolated from the CD95-deficient mice w ere found to be significantly more efficient than DC from control mice in t heir capacity to induce delayed type hypersensitivity responses in vivo. We propose that T cell-induced DC apoptosis serves as a unique down-regulator y mechanism that prevents the interminable activation of T cells by Ag-bear ing DC.