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.