The targeting of CD4+ T lymphocytes to a B cell lymphoma. A comparison of anti-CD3-anti-idiotype antibody conjugates and antigen-anti-idiotype antibody conjugates.
We have targeted CD4+ cytotoxic Th (Th/c) lymphocytes to a B cell lymphoma, through the use of a bispecific antibody containing binding sites for both the CD3 complex on the Th/c and the Id on the surface Ig of the B lymphoma (anti-CD3-anti-Id). Cloned, keyhole limpet hemocyanin (KLH)-specific Th/c cells were nonspecifically activated by the anti-CD3-anti-Id conjugate to lyse the Id+ B lymphoma A20-HL. This cytotoxicity was not inhibited by antibodies to CD4 or LFA-1 alpha molecules. The anti-CD3-anti-Id conjugates also induced non-lytic Th clones to become cytotoxic, a function not elicited when these cells were activated specifically by Ag. We compare this model to our previously described system where we targeted the KLH-specific Th/c cells to the Id+ B lymphoma A20-HL via a conjugate consisting of KLH covalently linked to the anti-Id antibody (KLH-anti-Id). The mechanism involved processing and presentation of KLH by the A20-HL target. This Ag-specific cytotoxicity was MHC class II restricted and was inhibited by antibodies to the CD4 molecule. In both systems, activation of the Th/c cells resulted in bystander killing of tumor but not normal targets. These results may have important implications for the use of Th/c cells in tumor immunotherapy.
Gravelle
M
M
Division of Molecular Immunology and Neurobiology, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.
Ochi
A
A
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000502:physiology; D000918:Antibody Specificity; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001667:Binding, Competitive; D017252:CD3 Complex; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006433:Hemocyanins / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007130:Immunoglobulin Idiotypes; D011948:Receptors, Antigen, T-Cell; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin