Soluble HLA-G and HLA-G1 expressing antigen-presenting cells inhibit T-cell alloproliferation through ILT-2/ILT-4/FasL-mediated pathways.
HLA-G is a tolerogenic molecule involved in maternal-fetal tolerance and in allograft acceptance. Soluble HLA-G proteins are present at high levels in plasma from transplanted patients who better accept their graft. In addition, infiltrating mononuclear cells expressing HLA-G can be detected within grafted tissues. To define the role of these HLA-G proteins in preventing graft rejection, we investigated the ability of HLA-G1 expressing antigen presenting cells (APC) and of soluble HLA-G proteins (i.e., HLA-G5 and shed HLA-G1) to inhibit T-cell alloproliferation and analyzed the molecules involved in such inhibition. Results demonstrated that both membrane-bound and soluble HLA-G proteins inhibited T-cell alloproliferation. This inhibition involved engagement of immunoglobulinlike transcript (ILT)-2 and ILT-4 receptors by HLA-G. Moreover, blocking Fas ligand (FasL) reversed HLA-G mediated inhibition, demonstrating that the Fas/FasL pathway is also recruited by HLA-G to exert its immunosuppressive function on T cells. These data highlight the role played by HLA-G in better graft acceptance status observed in transplanted patients with HLA-G(+) grafted cells and high HLA-G plasma levels. Evidence to support such role in vivo was provided by the capacity of purified HLA-G5 from the plasma of the transplanted patient to suppress T-cell alloresponses.
Naji
Abderrahim
A
Service de Recherches en Hemato-Immunologie, Hopital Saint-Louis, Institut Universitaire d'Hématologie, Paris, France.
Durrbach
Antoine
A
Carosella
Edgardo D
ED
Rouas-Freiss
Nathalie
N
D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000502:physiology*; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D053222:Fas Ligand Protein / Q000502:physiology*; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D006801:Humans; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D053222:Fas Ligand Protein; D006131:Growth Inhibitors; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; C491341:LILRB2 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic