B7-1 but not B7-2 efficiently costimulates CD8+ T lymphocytes in the P815 tumor system in vitro.
We recently have developed a method to generate primary P815-specific CTL in vitro from normal syngeneic splenocytes by employing transfection of B7-1 combined with exogenous IL-12 and IL-6. Surprisingly, when the homologous costimulator molecule B7-2 was substituted for B7-1 in this system, no specific CTL activity was obtained. Similarly, B7-1- but not B7-2-transfected P815 cells generated alloantigen-specific CTL activity from C57BL/6, accessory cell- and CD4(+)-depleted splenocytes, and costimulated proliferation of CD8+ lymphocytes in the presence of low doses of anti-CD3 mAb. In all systems, combined expression of both B7-1 and B7-2 costimulated as effectively as B7-1 alone, arguing against delivery of a dominant negative signal by B7-2. Proliferation of allogeneic, CD4(+)-depleted splenocytes in response to P815 cells, which relies on costimulation by normal accessory cells, was inhibited by anti-B7-1 but not anti-B7-2 mAbs. Finally, indirect evidence suggested a higher avidity of B7-1+ cells than B7-2+ cells for CTLA4. Thus, at least in the context of primary stimulation by irradiated P815 transfectants, B7-1 appears to be superior to B7-2 at costimulation of CD8+ T lymphocytes.
Ludwig Institute for Cancer Research, Brussels Branch, Catholic University of Louvain, Belgium.
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Gajewski
D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D000943:Antigens, Differentiation / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology / Q000502:physiology*; D051940:B7-2 Antigen; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D018796:Immunoconjugates; D018664:Interleukin-12 / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology; D007939:Leukemia L1210 / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000502:physiology*; D007959:Lymphocyte Culture Test, Mixed; D012515:Mast-Cell Sarcoma / Q000276:immunology / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D016853:Muromonab-CD3 / Q000494:pharmacology; D011994:Recombinant Proteins / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007376:Interleukin-2; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D016853:Muromonab-CD3; D011994:Recombinant Proteins; D018664:Interleukin-12; D000069594:Abatacept