Interactions between interferon γ and retinoic acid with transforming growth factor β in the induction of immune recognition molecules

Springer Science and Business Media LLC - Tập 37 - Trang 112-118 - 1993
Richard Darley1, Alan Morris2, James Passas2, Wendy Bateman2
1Department of Haematology, University of Cardiff, Wales, UK
2Department of Biological Sciences, University of Warwick, Coventry, UK

Tóm tắt

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 γ (IFNγ). Since transforming growth factor β (TGFβ) has been recently reported to antagonise HLA-DR induction by IFNγ we have examined, using a number of murine and human cell lines, the effect of TGFβ on IFNγ-induced MHC class I and class II and ICAM-1 expression. All of the cell lines tested expressed elevated class I MHC following IFNγ 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 TGFβ. TGFβ was found to antagonise IFNγ-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. TGFβ also inhibited induction of class I MHC expression by IFNα. However, TGFβ did not inhibit class I or class II MHC induction by IFNγ in any of the nine colorectal carcinoma cell lines, although two of five of the lines tested were growth-inhibited by TGFβ. On the other hand, human ICAM-1 induction by IFNγ was not affected by simultaneous treatment with TGFβ in any of the cell lines. The down-regulation of IFNγ-induced MHC antigens by TGFβ is not, therefore, the result of a general antagonism of IFNγ. 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 IFNγ-induced ICAM-1 expression, retinoic-acid-induced ICAM-1 expression was inhibited by TGFβ on two of the three responsive lines.

Tài liệu tham khảo

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