Prevention of graft-versus-host disease using antibody to Thy 1. A role for complement in vivo.
An in vitro assay was used to determine whether mouse complement (C') was able to lyse T cells coated with a monoclonal IgM anti-Thy-1 antibody. Using lymph node cells (LNC) as targets, it was found that antibody-coated mature T cells were efficiently lysed by serum from C57BL/6, but inefficiently lysed by serum from BALB/c mice. Serum from both strains lysed antibody-coated thymocytes, demonstrating that BALB/c serum is not deficient in one of the C' components. The lytic activity of BALB/c serum could be improved by increasing the concentration of monoclonal anti-Thy-1 used to coat the target LNC. In contrast, serum from C5-deficient A/HeJ mice was unable to lyse either of the antibody-coated target cells in vitro. These in vitro results were confirmed in vivo using a model of lethal graft-versus-host disease (GVHD) induced to minor histocompatibility antigens. In this model, GVHD occurs when lethally irradiated mice are transplanted with bone marrow plus spleen cells from H-2-identical donor mice. GVHD is prevented when T cells are removed from the cells by in vitro treatment with anti-Thy-1 antibody plus rabbit C'. As predicted by the in vitro data, C57BL/6 mice were protected from GVHD when transplanted with LP cells treated with a 1:100 dilution of anti-Thy-1 antibody, but without complement, but BALB/c recipients of antibody-coated B10.D2/nSN cells were not. When the concentration of anti-Thy-1 used to coat the donor cells was increased to 1:50, 8 of 9 recipients were protected from GVHD. In contrast, none of the C5-deficient DBA/2 recipients of anti-Thy-1 (1:50 dilution) treated B10.D2 cells were protected from GVHD. Complement-mediated lysis appears to be the primary mechanism by which T cells coated with a monoclonal IgM anti-Thy-1 antibody are functionally inactivated in vivo.
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D000818:Animals; D000954:Antigens, Surface / Q000276:immunology*; D003169:Complement Inactivator Proteins / Q000502:physiology; D003165:Complement System Proteins / Q000502:physiology*; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006461:Hemolysis; D007518:Isoantibodies / Q000502:physiology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008912:Minor Histocompatibility Loci; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018800:Thy-1 Antigens
D000954:Antigens, Surface; D003169:Complement Inactivator Proteins; D007518:Isoantibodies; D018800:Thy-1 Antigens; C035678:anti-Thy antibody; D003165:Complement System Proteins