International Immunology, Vol 9, 853-860, Copyright © 1997 by Oxford University Press
W Rudy, B Guckel, M Siebels, M Lindauer, SC Meuer and U Moebius
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.
ARTICLES
Differential function of CD80- and CD86-transfected human melanoma cells in the presence of IL-12 and IFN-gamma
Arbeitsgruppe Gentherapie von Tumoren, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
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