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 a means to augment the immunogenicity of tumor cells and to induce immune responses directed at tumor antigens. Here we compared CD80- and CD86-transfected human melanoma cells to induce primary immune responses by their capacity to promote proliferation of human allogeneic resting T lymphocytes. CD80- and CD86-transfected SkMel63 melanoma cells induced T cell activation to a comparable degree, which was found to be independent of the cell surface density of these co-stimulatory molecules. Co-expression of CD80 and CD86 did not result in a synergistic increase in T cell proliferation. Both CD80 and CD86 transfectants induced the proliferation of isolated CD4+ or CD8+ T cells. Exogenous IL-2, IL-4 and tumor necrosis factor-alpha respectively enhanced primary T cell proliferation independent of CD80 or CD86 expression. Interestingly, differential activities of CD80 and CD86 were observed following stimulation of resting T cells in the presence of IL-12. Whereas IL-12 increased T cell proliferation in the presence of CD86-transfected 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 not CD86-transfected SkMel63 cells and (III) the inhibitory effect of IL-12 was blocked by an anti-IFN-gamma mAb.
Rudy
W
W
Arbeitsgruppe Gentherapie von Tumoren, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Gückel
B
B
Siebels
M
M
Lindauer
M
M
Meuer
S C
SC
Moebius
U
U
D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D018122:B7-1 Antigen / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D051940:B7-2 Antigen; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology*; D018664:Interleukin-12 / Q000494:pharmacology*; D007399:Interphase / Q000235:genetics / Q000276:immunology; D007519:Isoantigens / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008545:Melanoma / Q000235:genetics* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D007166:Immunosuppressive Agents; D007519:Isoantigens; D008562:Membrane Glycoproteins; D018664:Interleukin-12; D007371:Interferon-gamma