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

• Published in: The Journal of immunology (1950) Vol. 162; no. 2; pp. 774 - 781
• Main Authors: Gorczynski, Laura, Chen, Z, Hu, J, Kai, Y, Lei, J, Ramakrishna, V, Gorczynski, R. M
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.01.1999
• Subjects: Adjuvants, Immunologic - pharmacology; Adoptive Transfer; AIDS/HIV; Animals; Antibodies, Monoclonal - pharmacology; Antigens, CD - analysis; Antigens, Surface - immunology; B7-1 Antigen - analysis; B7-2 Antigen; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; Cell Differentiation - immunology; Cells, Cultured; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Graft Survival - immunology; Immune Tolerance - immunology; Interleukin-2 - antagonists & inhibitors; Interleukin-2 - biosynthesis; Ligands; Liver - cytology; Liver - immunology; Lymphocyte Activation - immunology; Male; Membrane Glycoproteins - analysis; Membrane Proteins - pharmacology; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Spleen - cytology; Th1 Cells - immunology; Th1 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.2.774

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.