R. Darley et al., INTERACTIONS BETWEEN INTERFERON-GAMMA AND RETINOIC ACID WITH TRANSFORMING GROWTH-FACTOR-BETA IN THE INDUCTION OF IMMUNE RECOGNITION MOLECULES, Cancer immunology and immunotherapy, 37(2), 1993, pp. 112-118
The cell-surface expression of major histocompatibility (MHC) antigens
and the adhesion molecule intercellular adhesion molecule1 (ICAM-1) i
s essential for target cell recognition by T lymphocytes. The expressi
on of both classes of molecule is induced by various cytokines, notabl
y interferon gamma (IFNgamma). Since transforming growth factor beta (
TGFbeta) has been recently reported to antagonise HLA-DR induction by
IFNgamma we have examined, using a number of murine and human cell lin
es, the effect of TGFbeta on IFNgamma-induced MHC class I and class II
and ICAM-1 expression. All of the cell lines tested expressed elevate
d class I MHC following IFNgamma treatment. Class II MHC induction was
seen on most but not all of the cells, the exceptions being among a p
anel of human colorectal carcinoma cell lines. A striking difference b
etween cells of different origin was noted in the response to TGFbeta.
TGFbeta was found to antagonise IFNgamma-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 o
n MRC5 human fibroblasts and two human glioblastoma cell lines. Class
II MHC was much more strongly inhibited (sometimes completely) than cl
ass I MHC. TGFbeta also inhibited induction of class I MHC expression
by IFNalpha. However, TGFbeta did not inhibit class I or class II MHC
induction by IFNgamma in any of the nine colorectal carcinoma cell lin
es, although two of five of the lines tested were growth-inhibited by
TGFbeta. On the other hand, human ICAM-1 induction by IFNgamma was not
affected by simultaneous treatment with TGFbeta in any of the cell li
nes. The down-regulation of IFNgamma-induced MHC antigens by TGFbeta i
s not, therefore, the result of a general antagonism of IFNgamma. Reti
noic acid has recently been reported to induce ICAM-1 expression on hu
man tumour cells. We have confirmed this observation on MRC5, and the
two human glioblastoma cell lines, however six colorectal carcinoma ce
ll lines tested did not respond. In contrast to IFNgamma-induced ICAM-
1 expression, retinoic-acid-induced ICAM-1 expression was inhibited by
TGFbeta on two of the three responsive lines.