Differential function of CD80- and CD86-transfected human melanoma cells in the presence of IL-12 and IFN-gamma

Introduction of co-stimulatory molecules like CD80 and CD86 represents ameans to augment the immunogenicity of tumor cells and to induce immuneresponses directed at tumor antigens. Here we compared CD80- andCD86-transfected human melanoma cells to induce primary immune responses bytheir capacity to promote proliferation of human allogeneic resting Tlymphocytes. CD80- and CD86-transfected SkMel63 melanoma cells induced Tcell activation to a comparable degree, which was found to be independentof the cell surface density of these co- stimulatory molecules.Co-expression of CD80 and CD86 did not result in a synergistic increase inT cell proliferation. Both CD80 and CD86 transfectants induced theproliferation of isolated CD4+ or CD8+ T cells. Exogenous IL-2, IL-4 andtumor necrosis factor-alpha respectively enhanced primary T cellproliferation independent of CD80 or CD86 expression. Interestingly,differential activities of CD80 and CD86 were observed followingstimulation of resting T cells in the presence of IL-12. Whereas IL-12increased T cell proliferation in the presence of CD86-transfected melanomacells, it exhibited an inhibitory function in the presence ofCD80-expressing SkMel63 cells. Experimental evidence indicates that thisinhibitory effect was mediated by IFN- gamma since (I) IFN-gamma secretionof stimulated T cells was augmented by IL-12, (II) exogenous IFN-gamma alsoinhibited T cell proliferation induced by CD80- but not CD86-transfectedSkMel63 cells and (III) the inhibitory effect of IL-12 was blocked by ananti-IFN-gamma mAb.