DIFFERENTIAL FUNCTION OF CD80-TRANSFECTED 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 a means to augment the immunogenicity of tumor cells and to induce im mune responses directed at tumor antigens, Here we compared CD80- and CD86-transfected human melanoma cells to induce primary immune respons es by their capacity to promote proliferation of human allogeneic rest ing T lymphocytes, CD80- and CD86-transfected SkMel63 melanoma cells i nduced T cell activation to a comparable degree, which was found to be independent of the cell surface density of these co-stimulatory molec ules. Co-expression of CD80 and CD86 did not result in a synergistic i ncrease in T cell proliferation. Both CD80 and CD86 transfectants indu ced the proliferation of isolated CD4(+) or CD8(+) T cells. Exogenous IL-2, IL-4 and tumor necrosis factor-alpha respectively enhanced prima ry T cell proliferation independent of CD80 or CD86 expression, Intere stingly, differential activities of CD80 and CD86 were observed follow ing stimulation of resting T cells in the presence of IL-12, Whereas I L-12 increased T cell proliferation in the presence of CD86-transfecte d melanoma cells, it exhibited an inhibitory function in the presence of CD80-expressing SkMel63 cells, Experimental evidence indicates that this inhibitory effect was mediated by IFN-gamma since (i) IFN-gamma secretion of stimulated T cells was augmented by IL-12, (ii) exogenous IFN-gamma also inhibited T cell proliferation induced by CD80- but no t CD86-transfected SkMel63 cells and (iii) the inhibitory effect of IL -12 was blocked by an anti-IFN-gamma mAb.