The Regulation of Major Histocompatibility Complex (MHC) Antigen and Tumor Associated Antigens (TAAs) by Interleukin-10

Tumor cells can escape from the host's protective immune system: Natural Killer （NK） cells, Cytotoxic T cell lymphocyte （CTL）, etc. The inhibitory cytokines, such as interleukin-4 （IL-4）, interleukin-10 （IL-10）, transforming growth factor-β （TGF-β）, etc, have been reported to be involved in the mechanism of this escape. Although the effect of inhibitory cytokines on effector cells are well investigated, that on tumor cells is little known. We therefore investigated how IL-10 effects tumor cells using both W31 cells which were the H-ras mediated transformant of WFB （a WKA rat fetus-derived fibroblast cell line）, and WMT-55, the polyoma middle T-mediated transformant of WFB. The above cells have Tumor Associated Antigens （TAAs）, such as NK target structure （NKTS） and heat shock cognate （hsc）, and are NK-sensitive. Cells were incubated for 3 days with rhIL-10 at different concentrations, and FACS analysis was performed. Then, following pretreatment of cells with rhIL-10 for 3 days, 51Cr release assay was performed. In this study, we revealed that IL-10 downregulated the expression of the NK target structure, reduced NK sensitivity, and downregulated the expression of MHC class I, which probably facilitated the tumor cells' escape from the attack of the CTL. In addition, IL-10 downregulated the ?expression of heat shock protein which either 1）, constituted a relay line in which the peptides were generated in the cytosol by the action of the proteases, until they were finally accepted by MHC class I molecules in the endoplasmic reticulum; or 2）, bound to peptides that expressed themselves on the cell surface. In other words, IL-10 downregulated the processing of peptides and the presentation of antigens. These effects of IL-10 are very important in an analysis of the mechanism by which the tumor cells escape from protective immune responses.departmental bulletin pape