Antilymphocytic antibodies and marrow transplantation. IX. T-cell depletion in marrow donors with C1q high and low affinity antibodies for suppression of GVHD in fully mismatched mice.
Rat monoclonal antibodies (mAbs) of the same specificity (anti-Thy-1) but different immunoglobulin (Ig) subclass were investigated for their effect on suppression of graft-versus-host disease (GVHD) by depleting the marrow donors of T cells in vivo. Transplantation to homozygous, fully mismatched mice of spleen and bone marrow cells from unthymectomized mice injected with the mAbs revealed that two rat anti-Thy-1 mAbs with high affinity for C1q (IgG2b) suppressed and prevented acute and chronic mortality of GVHD. In contrast, rat mAbs with low affinity for C1q (IgM, IgG2c) barely delayed acute mortality. This correlated with findings on the degree of splenic T-cell depletion in donor mice with the IgG2b mAb, able to deplete 97%, and the IgG2c and IgM mAbs, only 83% and 75% of T cells, respectively. An effect akin to the one achieved with IgG2b was seen, however, when donor mice were thymectomized and then treated with three injections of IgG2c isotype. The rat IgM mAb was not immunosuppressive even under such conditions. Immunocytochemical and immunohistochemical examination of the donor lymph nodes after single injection of either mAb showed that only 84% of T cells were eliminated, and in contrast to the spleen, none of the tested antibodies could deplete T cells further. The thymus did not appear depleted at all, although the cortical thymocytes were coated with either of the injected mAbs.
Antica
M
M
Institute of Immunology, GSF, Munich, Federal Republic of Germany.
Hoffmann-Fezer
G
G
Thierfelder
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D000954:Antigens, Surface / Q000276:immunology; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D003166:Complement Activating Enzymes / Q000276:immunology*; D003172:Complement C1 / Q000276:immunology*; D015922:Complement C1q; D006086:Graft vs Host Disease / Q000517:prevention & control*; D007132:Immunoglobulin Isotypes / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018800:Thy-1 Antigens; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D003172:Complement C1; D007132:Immunoglobulin Isotypes; D018800:Thy-1 Antigens; D015922:Complement C1q; D003166:Complement Activating Enzymes