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Dendritic cells (DC) play critical roles in generating an immune response and in inducing tolerance. Diverse microenvironmental factors can 'polarize' DC toward an immunogenic or non-immunogenic phenotype. Among the various microenvironmental factors, interleukin-10 (IL-10) exhibits a potent immunosuppressive effect on antigen-presenting cells (APC). Here, we show that monocyte-derived DC generated in the presence of IL-10 exhibit a profound down-regulation of many genes that are associated with immune activation and show that the IL-10-grown DC are poor stimulators of CD8(+) T cells in a strictly autologous and major histocompatibility complex (MHC) class I-restricted melanoma antigen recognized by T cells (MART-1) epitope presentation system. However, these IL-10-grown DC can efficiently activate the epitope-specific CD8(+) T cells when they are made to present the epitope following transduction with an adenoviral vector expressing the MART-1 antigen. In addition, we show that the MART-1 protein colocalizes with the MHC class I protein, equally well, in the iDC and in the DC cultured in presence of IL-10 when both DC types are infected with the viral vector. We also show that the vector transduced DC present the MART-1(27-35) epitope for a sustained period compared to the peptide pulsed DC. These data suggest that although DCs generated in the presence of IL-10 tend to be non-immunogenic, they are capable of processing and presenting an antigen when the antigen is synthesized within the DC.

The effect of solube antigens from polyoma tumor cells, liver antigens and PHA on lymph node cells from tumor bearers and on normal lymph node cells in CBA mice was studied. The stimulation index was calculated on the basis of incorporation of 14C-leucine in short-term cultures. The stimulation index was lower in lymphocytes derived from tumor bearers than those from normal donors. The blastoid responses to polyoma-associated antigens and PHA were similar, in contrast to liver-associated antigens. It was concluded that stimulation of liver antigens may be connected with different chemical structure, mainly of carbohydrate components.