INTERFERON-GAMMA IMPAIRS THE ABILITY OF MONOCYTE-DERIVED DENDRITIC CELLS TO PRESENT TUMOR-SPECIFIC AND ALLO-SPECIFIC ANTIGENS AND REDUCES THEIR EXPRESSION OF CD1A, CD80 AND CD4

Dendritic cells (DC), the most potent antigen-presenting cells found t o date, can be generated from the adherent fraction of peripheral bloo d mononuclear cells (PBMC) by culture with granulocyte-macrophage colo ny-stimulating factor (GM-CSF) and IL-4, When interferon gamma (IFN-ga mma) was added to the culture medium, the expression of CD1a, CD4 and CD80 markers were significantly reduced, while that of HLA-A, B, C, MH C II (MHC-DR), CD11a and CD54 were increased. T cell proliferation ana lysis showed that the DC derived from monocytes cultured with GM-CSF, IL-4 and IFN-gamma only induced weak responses in both activated and n aive allogeneic CD4(+) and CD8(+) T cells when compared to the reactio n elicited by DC cultured without IFN-gamma. Furthermore, the DC deriv ed from cultures with IFN-gamma, loaded with an immunogenic peptide de rived from the HER2/neu protein [HER2 (9(466))], only induced low leve ls of TNF release and weak proliferative responses in a specific cytot oxic CD8(+) T lymphocyte clone. Therefore, our results indicate that I FN-gamma negatively influences the differentiation and function of mon ocyte-derived DC by affecting the expression of surface molecules invo lved in their antigen-presenting function. This supports the general h ypothesis that there exists a feedback immune regulatory mechanism bet ween T cells and monocytes/DC. (C) 1998 Academic Press.