Evidence that an OX-2-positive cell can inhibit the stimulation of type 1 cytokine production by bone marrow-derived B7-1 (and B7-2)-positive dendritic cells

We reported that hepatic mononuclear, nonparenchymal cells (NPC) can inhibi t the immune response seen when allogeneic C57BL/6 dendritic cells (DC) are incubated with C3H spleen responder cells. Cells derived from these cultur es transfer increased survival of C57BL/6 renal allografts in C3H mice. We also found that increased expression of OX-2 on DC was associated with inhi bition of cytokine production and renal allograft rejection. We explored wh ether inhibition by hepatic NPC was a function of OX-2 expression by these cells. Fresh C57BL/6 spleen-derived DC were cultured with C3H spleen respon der cells and other putative coregulatory cells. The latter were derived fr om fresh C3H or C57BL/6 liver NPC, or from C3H or C57BL/6 mice treated for 10 days by i.v. infusion of human Flt3 ligand, Different populations of mur ine bone marrow-derived DC from cultures of bone marrow with IL-4 plus gran ulocyte macrophage-CSF were also used as a source of putative regulator cel ls. Supernatants of all stimulated cultures were examined for functional ex pression of different cytokines (IL-2, IL-4, IFN-gamma, and TGF beta). We f ound that fresh C57BL/6 splenic DC induced IL-2, not IL-4, production, Cell s from the sources indicated inhibited IL-2 and IFN-gamma production and pr omoted IL-4 and TGF beta production. Inhibition was associated with increas ed expression of OX-2 on these cells, as defined by semiquantitative PCR an d FAGS analysis. By size fractionation, cells expressing OX-2 were a subpop ulation of NLDC145(+) cells. Our data imply a role for cells expressing OX- 2 in the regulation of induction of cytokine production by conventional all ostimulatory DC.