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 inhibit the immune response seen when allogeneic C57BL/6 dendritic cells (DC) are incubated with C3H spleen responder cells. Cells derived from these cultures 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 inhibition of cytokine production and renal allograft rejection. We explored whether 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 responder cells and other putative coregulatory cells. The latter were derived from 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 murine bone marrow-derived DC from cultures of bone marrow with IL-4 plus granulocyte-macrophage-CSF were also used as a source of putative regulator cells. Supernatants of all stimulated cultures were examined for functional expression of different cytokines (IL-2, IL-4, IFN-gamma, and TGFbeta). We found that fresh C57BL/6 splenic DC induced IL-2, not IL-4, production. Cells from the sources indicated inhibited IL-2 and IFN-gamma production and promoted IL-4 and TGFbeta production. Inhibition was associated with increased expression of OX-2 on these cells, as defined by semiquantitative PCR and FACS analysis. By size fractionation, cells expressing OX-2 were a subpopulation of NLDC145+ cells. Our data imply a role for cells expressing OX-2 in the regulation of induction of cytokine production by conventional allostimulatory DC.