Protective Immunity Induced by Tumor Vaccines Requires Interaction between CD4Oand Its Ligand,CD1541

Interactions between CD4O and its ligand, CD1S4 (CD4OL, gp39), have been shown to play a central role in the regulation of humoral immunity. Recent evidence suggests that this ligand-receptor pair also plays an important role in the induction of cell-mediated immune responses, in cluding those directed against viral pathogens, intracellular parasites, and alloantigens. The contribution of this ligand-receptor pair to the develop meat of protective immunity against syngeneic tumors was evaluated by blockingthe in vivofunction of CD1S4or by studying tumor resistancein mice genetically deficient in CD4O expression (CD40'). In the former case, anti-CD1S4 monoclonal antibody treatment inhibited the generation of protective immune responses after the administration of three potent tumor vaccines: irradiated MCA 105, MCA 105 admixed with Coryne bacterium parvum adjuvant, and irradiated B16 melanoma cells tram duced with the gene for granulocyte macrophage colony-stimulating fac tsr. Confirmation of the role of CD4O/CD1S4 interactions in tumor immunity was provided by the overt tumor susceptibility in CD4O-defi cleat mice as compared to that in CD4O@ mice. In this case, wild-type but not CD4O-deficientmice could be readily protected against live TWA tumor challenge by preimmunization with 1'S/A admixed with C. parvum. These findings suggest a critical role for CD4O/CDIS4 interactions in the induction of cellular immUnity by tumor vaccines and may have impor tant Implications for future approaches to cell-based cancer therapies.