Darley R, Morris A, Passas J, Bateman W
Department of Biological Sciences, University of Warwick, Coventry, UK.
Cancer Immunol Immunother. 1993 Jul;37(2):112-8. doi: 10.1007/BF01517043.
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.
主要组织相容性（MHC）抗原和黏附分子细胞间黏附分子1（ICAM-1）在细胞表面的表达对于T淋巴细胞识别靶细胞至关重要。这两类分子的表达均由多种细胞因子诱导，尤其是干扰素γ（IFNγ）。由于最近报道转化生长因子β（TGFβ）可拮抗IFNγ诱导的HLA-DR表达，我们使用多种小鼠和人类细胞系研究了TGFβ对IFNγ诱导的MHC I类和II类以及ICAM-1表达的影响。所有测试的细胞系在IFNγ处理后I类MHC表达均升高。大多数但并非所有细胞都出现了II类MHC诱导，例外情况存在于一组人类结肠癌细胞系中。在对TGFβ的反应中，不同来源的细胞存在显著差异。发现TGFβ可拮抗IFNγ诱导的C3H 10T1/2小鼠成纤维细胞、早期传代的BALB/c小鼠胚胎成纤维细胞、一种小鼠少突胶质细胞瘤细胞系以及MRC5人类成纤维细胞和两种人类胶质母细胞瘤细胞系上的I类和II类MHC表达。II类MHC受到的抑制比I类MHC更强（有时完全被抑制）。TGFβ还抑制IFNα诱导的I类MHC表达。然而，在九个结肠癌细胞系中的任何一个中，TGFβ均未抑制IFNγ诱导的I类或II类MHC表达，尽管所测试的五个细胞系中有两个受到TGFβ的生长抑制。另一方面，在任何细胞系中，TGFβ同时处理均不影响IFNγ诱导的人类ICAM-1表达。因此，TGFβ对IFNγ诱导的MHC抗原的下调并非IFNγ普遍拮抗的结果。最近报道维甲酸可诱导人类肿瘤细胞上的ICAM-1表达。我们已在MRC5和两种人类胶质母细胞瘤细胞系上证实了这一观察结果，然而所测试的六个结肠癌细胞系没有反应。与IFNγ诱导的ICAM-1表达相反，在三个有反应的细胞系中的两个中，维甲酸诱导的ICAM-1表达受到TGFβ的抑制。
