CD4+ T cells appear capable of initiating graft-versus-host disease across non-major histocompatibility complex (MHC) barriers in man.
Twelve patients with haematological malignancy received cyclophosphamide 120 mg/kg, fractionated total body irradiation 12 Gy, oral cyclosporin and an HLA-identical sibling marrow transplant depleted of T cells by incubation with monoclonal antibodies directed against the CD2 and CD8 antigens and rabbit complement. The phenotype of the residual T cells in the donor marrow inocula was CD3+, CD4+, CD8-. To exclude the possibility that this represented modulation or blocking of the CD8 antigen, T-depleted and non-depleted marrow aliquots from these donors were bulk-cultured for 10 days with phytohaemagglutinin and interleukin-2. Even after this attempted expansion, only a small proportion of cultured T cells from the depleted aliquots (in contrast to the non-depleted aliquots) expressed the CD8 antigen. Since all patients receiving CD3+, CD4+, CD8- marrow developed mild or moderate acute graft-versus-host disease (GVHD), we conclude that CD4+ T cells are capable of initiating acute GVHD across non-MHC barriers in man.
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D018801:CD2 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology*; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008285:Major Histocompatibility Complex; D010835:Phytohemagglutinins / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000032:analysis
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D016827:CD8 Antigens; D006680:HLA Antigens; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic