Transforming growth factor-beta 1 modulates the expression of class II histocompatibility antigens on human cells.
We have examined the effects of transforming growth factor-beta (TGF-beta 1) on the expression of the class II histocompatibility Ag, HLA-DR: 1) induced by human rIFN-gamma (rHuIFN-gamma) in human melanoma, Hs294T cells and 2) constitutively expressed in a subclone Hs294T cell line. The expression of HLA-DR Ag on Hs294T cells was induced by rHuIFN-gamma in a dose- and time-dependent manner with maximal levels obtained with 10 ng/ml rHuIFN-gamma after 48 h exposure. Treatment of Hs294T cells with natural porcine platelet-derived or human rTGF-beta 1 (1 to 100 ng/ml) in the presence of rHuIFN-gamma (0.1 to 10 ng/ml) reduced the percentage of cells positive for this Ag by approximately 40 to 50%, as determined by flow cytometry. This suppressive effect of TGF-beta 1 was not restricted to Hs294T cells inasmuch as rHuIFN-gamma induced HLA-DR surface Ag expression on PBMC-derived adherent cells was also significantly inhibited by TGF-beta 1. Northern blot analysis of cytoplasmic RNA extracted from Hs294T cells indicated that the decreased levels of HLA-DR cell-surface Ag correlated with decreased levels of mRNA transcripts encoding this Ag. TGF-beta 1 also effectively reduced the levels of HLA-DR mRNA in 1) cells that had been pretreated with rHuIFN-gamma and were expressing maximal levels of HLA-DR surface antigen and 2) cells that constitutively expressed HLA-DR surface Ag without exogenous rHuIFN-gamma treatment.
D000954:Antigens, Surface / Q000096:biosynthesis; D002460:Cell Line; D006681:HLA-D Antigens / Q000096:biosynthesis*; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D015291:Transforming Growth Factors; D014407:Tumor Cells, Cultured / Q000276:immunology* / Q000378:metabolism
D000954:Antigens, Surface; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015291:Transforming Growth Factors; D007371:Interferon-gamma