Dendritic cells (DC), the most potent antigen-presenting cells found to date, can be generated from the adherent fraction of peripheral blood mononuclear cells (PBMC) by culture with granulocyte–macrophage colony-stimulating factor (GM-CSF) and IL-4. When interferon gamma (IFN-γ) was added to the culture medium, the expression of CD1a, CD4 and CD80 markers were significantly reduced, while that of HLA-A, B, C, MHC II (MHC-DR), CD11a and CD54 were increased. T cell proliferation analysis showed that the DC derived from monocytes cultured with GM-CSF, IL-4 and IFN-γ only induced weak responses in both activated and naive allogenic CD4⁺and CD8⁺T cells when compared to the reaction elicited by DC cultured without IFN-γ. Furthermore, the DC derived from cultures with IFN-γ, loaded with an immunogenic peptide derived from the HER2/neu protein [HER2 (9₄₆₆)], only induced low levels of TNF release and weak proliferative responses in a specific cytotoxic CD8⁺T lymphocyte clone. Therefore, our results indicate that IFN-γ negatively influences the differentiation and function of monocyte-derived DC by affecting the expression of surface molecules involved in their antigen-presenting function. This supports the general hypothesis that there exists a feedback immune regulatory mechanism between T cells and monocytes/DC.