Interactions between interferon gamma and retinoic acid with transforming growth factor beta in the induction of immune recognition molecules.

The cell-surface expression of major histocompatibility (MHC) antigens and the adhesion molecule intercellular adhesion molecule 1 (ICAM-1) is essential for target cell recognition by T lymphocytes. The expression of both classes of molecule is induced by various cytokines, notably interferon gamma (IFN gamma). Since transforming growth factor beta (TGF beta) has been recently reported to antagonise HLA-DR induction by IFN gamma we have examined, using a number of murine and human cell lines, the effect of TGF beta on IFN gamma-induced MHC class I and class II and ICAM-1 expression. All of the cell lines tested expressed elevated class I MHC following IFN gamma treatment. Class II MHC induction was seen on most but not all of the cells, the exceptions being among a panel of human colorectal carcinoma cell lines. A striking difference between cells of different origin was noted in the response to TGF beta. TGF beta was found to antagonise IFN gamma-induced class I and class II MHC expression on C3H 10T1/2 murine fibroblasts, early-passage BALB/c mouse embryo fibroblasts, a murine oligodendroglioma cell line, and on MRC5 human fibroblasts and two human glioblastoma cell lines. Class II MHC was much more strongly inhibited (sometimes completely) than class I MHC. TGF beta also inhibited induction of class I MHC expression by IFN alpha. However, TGF beta did not inhibit class I or class II MHC induction by IFN gamma in any of the nine colorectal carcinoma cell lines, although two of five of the lines tested were growth-inhibited by TGF beta. On the other hand, human ICAM-1 induction by IFN gamma was not affected by simultaneous treatment with TGF beta in any of the cell lines. The down-regulation of IFN gamma-induced MHC antigens by TGF beta is not, therefore, the result of a general antagonism of IFN gamma. Retinoic acid has recently been reported to induce ICAM-1 expression on human tumour cells. We have confirmed this observation on MRC5, and the two human glioblastoma cell lines, however six colorectal carcinoma cell lines tested did not respond. In contrast to IFN gamma-induced ICAM-1 expression, retinoic-acid-induced ICAM-1 expression was inhibited by TGF beta on two of the three responsive lines.