Transplant tolerance modifying antibody to CD200 receptor, but not CD200, alters cytokine production profile from stimulated macrophages.
Increased C57BL/6 allograft survival following donor-specific dendritic cell (DC) portal vein (pv) pre-transplant immunization of C3H mice is associated with increased expression of the molecule CD200 on DC, delivery of suppressive signals by CD200(r+) macrophages, and polarization in cytokine production towards type-2 cytokines. Infusion of anti-mouse CD200 monoclonal antibody abolishes these effects. We have used whole Ig, and F(ab')(2) fragments, of anti-CD200 and anti-CD200(r) mAb to explore the relative signaling role of CD200(+) versus CD200(r+) cells in suppression of type-1 cytokine production in mixed leukocyte cultures (MLC), and enhanced graft survival in vivo. Simple neutralization of CD200 [even by F(ab')(2) antibody] reversed CD200-mediated suppression. However, only whole anti-CD200(r) antibody was effective in stimulating suppression from CD200(r+) cells. Suppression of cytokine induction following cross-linking of CD200(r+) cells in vitro was attenuated by anti-IL-6 mAb. Our data are consistent with the hypothesis that CD200(r) itself delivers the crucial intracellular signal leading to immunosuppression, a feature likely of importance in autoimmunity and transplantation.
Gorczynski
R M
RM
CCRW 2-855, The Toronto Hospital, University Health Network, Toronto, Ontario, Canada.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D017353:Gene Deletion; D006085:Graft Survival / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011169:Portal Vein; D015398:Signal Transduction; D016038:Skin Transplantation / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D007140:Immunoglobulin Fab Fragments; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma