Neutralization of immunosuppression by antibodies against variable as well as constant regions of monoclonal anti-Thy-1 xenoantibodies and their ability to be suppressed by initial T cell depletion.
Timing, magnitude, and effect of the murine antibody response to rat pan-T-cell antibodies were studied in a bone marrow (C57BL/6-to-CBA mice) transplantation model. Prospective C57BL/6 marrow donor mice were sensitized against pan-T-cell (Thy-1, Thy-1.2, Lyt-1) monoclonal antibodies of various rat isotypes or against polyclonal rat antimouse-thymocytes (rat ATG) antibodies. Three days prior to transfer of spleen and bone marrow cells, the sensitized C57BL/6 donors received a dose of anti-Thy-1 mAb (RmT1) known to abolish graft-versus-host reactivity of unsensitized donors. The injected mAb provoked anti-antibodies reacting with RmT1. The anti-antibodies inhibited immunosuppression of the rat mAb RmT1 even if they bound only to nonidiotypic epitopes on RmT1. Avoiding cell-binding of the sensitizing rat anti-Thy-1.2 mAb by its injection into Thy-1.1 mice induced only low-titer and delayed anti-antibodies. This indicated the enhanced immunization potential of anti-Thy-1 when bound to cells. Finally, sensitization leading to the mouse antirat anti-antibodies and reversion of immunosuppression was prevented or reduced considerably by T cell depletion with a mouse IgG2a anti-Thy-1.2 mAb or high-dose cyclophosphamide or by rabbit ATG, provided it was initiated before starting the sensitizing injections of the rat antimouse T cell antibodies.
Kremmer
E
E
Institut für Immunologie, GSF, München, Federal Republic of Germany.
Thierfelder
S
S
Kummer
U
U
Lederer
R
R
Mysliwietz
J
J
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D000939:Epitopes; D006086:Graft vs Host Disease / Q000517:prevention & control; D007108:Immune Tolerance; D007127:Immunoglobulin Constant Regions / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D007127:Immunoglobulin Constant Regions; D007135:Immunoglobulin Variable Region; D018800:Thy-1 Antigens