HLA-DR restriction in suppression of hematopoiesis by T cells from allogeneic bone marrow transplants.
Three allogeneic bone marrow transplantation patients who exhibited a suppressive subset of T cells for in vitro hematopoiesis have been investigated to determine whether this T cell suppressive effect was genetically restricted. In the three cases, T cells separated by sheep red cell rosetting inhibited blood colony-forming units granulocyte-monocyte (CFU-GM) and burst-forming unit erythroid (BFU-E) growth from the patients and from the bone marrow donors who were HLA identical, but not from randomly chosen unrelated subjects. In one case, cocultures were performed between the patient T cells and the T-depleted cells from eight siblings and from the mother. A marked inhibition (30 to 60%) of CFU-GM and BFU-E growth was found in the relatives who shared a haplo-identical HLA-DR 5. The same degree of suppression was found with respect to whether the siblings were homozygous or heterozygous for the HLA-DR 5 antigen, and whether or not they shared common class I antigens. This inhibition was totally abolished when a monoclonal antibody against HLA-DR was added, whereas a monoclonal antibody against class I histocompatibility antigen had no effect. To additionally demonstrate that this inhibition was mediated by a single HLA-DR haplotype, T cells from the patient were co-cultured with cells from three normal unrelated individuals, one with a phenotypically identical DR and two with only one haploidentical DR. Inhibition was similarly found in the subject exhibiting complete DR identity, and the subject with only the DR 5 haploidentical phenotype. These results demonstrate that a unique subset of T cells present in allogeneic bone marrow transplants specifically suppress differentiation of hemopoietic progenitors that bear one phenotypically haplo-identical HLA-DR antigen.
D000328:Adult; D016026:Bone Marrow Transplantation; D002455:Cell Division; D004912:Erythrocytes / Q000166:cytology; D005260:Female; D006098:Granulocytes / Q000166:cytology; D006684:HLA-DR Antigens; D006410:Hematopoiesis; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000166:cytology; D008297:Male; D011897:Random Allocation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000502:physiology; D014184:Transplantation, Homologous
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II