Alloreactive CD4+ and CD8+ T cells express the immunotolerant HLA-G molecule in mixed lymphocyte reactions: in vivo implications in transplanted patients.
HLA-G displays immunotolerogenic properties towards the main effector cells involved in graft rejection through inhibition of NK- and CTL-mediated cytolysis and CD4+ T cell alloproliferation. HLA-G expression is restricted in healthy tissues to trophoblast and thymus but is extended to various tissues under pathological conditions. HLA-G was detected in allograft biopsies and sera from transplanted patients who displayed a better graft acceptance. However, the cells involved in such de novo expression of HLA-G remain to be characterized. By flow cytometry and confocal microscopy, we demonstrated that, following allogeneic stimulation in vitro, both CD4+ and CD8+ T cell subsets can express membrane-bound HLA-G1 and/or soluble HLA-G5 molecules. Such HLA-G1/-G5 expression is regulated at the transcriptional level. Soluble HLA-G5 could be detected by using a novel monoclonal antibody, 5A6G7, specific for the intron 4-retaining sequence of HLA-G5. Finally, the biological relevance of these data was provided by analysis of transplanted patients in whom we identified both CD4+ and CD8+ T cells expressing HLA-G. The HLA-G-positive T cells we describe here may constitute a cellular source of HLA-G after allotransplantation and may be involved in the improved graft acceptance which is observed in HLA-G-positive transplanted patients.
Service de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Paris, France.
Solène
S
Le Rond
Service de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Paris, France.
Joël
J
Le Maoult
Service de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Paris, France.
Caroline
C
Créput
Service de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Paris, France.
Catherine
C
Menier
Service de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Paris, France.
Marina
M
Deschamps
Laboratoire Universitaire d'Hématologie et de la Biologie des Cellules Sanguines, UPRES EA 2233, Faculté de Médecine, Université Rennes I, Rennes, France.
Gaëlle
G
Le Friec
Laboratoire Universitaire d'Hématologie et de la Biologie des Cellules Sanguines, UPRES EA 2233, Faculté de Médecine, Université Rennes I, Rennes, France.
Laurence
L
Amiot
Département de Néphrologie, Hôpital du Kremlin-Bicêtre, Le Kremlin-Bicêtre, France.
Antoine
A
Durrbach
Fondation Jean Dausset, CEPH, Paris, France.
Jean
J
Dausset
Service de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Paris, France.
Edgardo D
ED
Carosella
Service de Recherches en Hémato-Immunologie, CEA-DSV-DRM, Hôpital Saint-Louis, IUH, Paris, France.
Nathalie
N
Rouas-Freiss
D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D023001:Transplantation Tolerance
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007519:Isoantigens; D020033:Protein Isoforms; D012333:RNA, Messenger