Specific inhibition of CD4+ T lymphocytes by a hybrid antibody.
T lymphocytes are crucial in the defense against foreign intruders and cancerous growths. Yet, in circumstances such as transplantation or autoimmunity, T-cell-mediated responses can be detrimental. Inhibition of these deleterious responses is currently achieved by drugs that induce general immune suppression. These compounds also impair the patient's defenses against infections. Strategies are now being sought that induce selective rather than generalized immune unresponsiveness. One such strategy is the ability to inhibit the activation of CD8+ T lymphocytes. As CD4+ T lymphocytes similarly participate in graft rejection and in autoimmune diseases, we have now developed a reagent to delete their activity. It comprises CD4 and an anti-MHC class II antibody. By virtue of the antibody's specificity for MHC class II molecules, this hybrid antibody (Hab) binds to class II molecules, thereby bringing CD4 accessory molecules to the surface of class II-bearing stimulator cells where they occupy CD4 binding sites on class II molecules. As a consequence CD4+ T cells with specificity to Hab-coated stimulator cells cannot engage their CD4 molecules and are no longer activated. This Hab technology provides a strategy to offer specific rather than generalized immune suppression.
Qi
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Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Staerz
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D000818:Animals; D018033:Antibodies, Bispecific / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D003602:Cytotoxicity, Immunologic; D005260:Female; D005802:Genes, MHC Class II; D007165:Immunosuppression Therapy; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000528:radiation effects
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D003432:Cross-Linking Reagents; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins