Generation of protective immunity against an immunogenic carcinoma requires CD40/CD40L and B7/CD28 interactions but not CD4(+) T cells.
Interactions between CD40 and CD40L play a central role in the regulation of both humoral and cellular immunity. Recently, interactions between these molecules have also been implicated in the generation of protective cell-mediated tumor immunity. We have generated a tumor model in which a well-understood and clearly immunostimulatory antigen, influenza hemagglutinin has been transfected into the BALB/c-derived, MHC-class-I-positive, B7-deficient murine mammary carcinoma, MT901. In this model, expression of the influenza hemagglutinin antigen does not alter tumorigenicity in naïve but serves as a tumor-rejection target in immunized mice. T-cell-depletion experiments indicate that successful tumor protection can occur following immunization in mice depleted of CD4(+) but not CD8(+) T cells, suggesting that tumor protection is largely CD8-mediated and CD4-independent. Interestingly, despite the ability of tumor protection to be generated in the absence of CD4(+) T cells, effective immunization was clearly dependent on CD40/CD40L as well as CD28/B7 interactions.
Eck
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Department of Medicine, University of Pennsylvania, 901 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104-6100, USA.
Turka
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D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology; D018122:B7-1 Antigen / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology; D007114:Immunization; D018796:Immunoconjugates; D008212:Lymphocyte Depletion; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D006389:Hemagglutinins, Viral; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D023201:CD40 Ligand; D000069594:Abatacept