Nakazawa A, Watanabe M, Kanai T, Yajima T, Yamazaki M, Ogata H, Ishii H, Azuma M, Hibi T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Gastroenterology. 1999 Sep;117(3):536-45. doi: 10.1016/s0016-5085(99)70446-4.
BACKGROUND & AIMS: Costimulatory signals are essential for T-cell activation. The aim of this study was to demonstrate expression of costimulatory molecules CD86 and CD80 in human colonic epithelial cells and assess their functional roles in the activation of T cells in inflamed colonic mucosa.
CD86 and CD80 expression was assessed by immunohistochemistry of colonic mucosa, reverse-transcription polymerase chain reaction, and flow cytometric analysis of isolated colonic epithelial cells and cell lines. Costimulatory effect of CD86-expressing colonic epithelial cells on purified CD4(+) T-cell proliferation was also assessed at suboptimal phytohemagglutinin stimulation.
CD86 and CD80 messenger RNA was detected in isolated colonic epithelial cells from normal and inflamed mucosa of patients with ulcerative colitis. Immunohistochemistry and flow cytometric analysis of colonic epithelial cells confirmed cell surface expression of CD86 protein in inflamed colonic mucosa. Cell surface expression of CD86 protein was increased in the colonic epithelial cell line HT29-18-N2 after interferon gamma stimulation. Purified CD4(+) T cells proliferated in response to suboptimal phytohemagglutinin costimulated with interferon gamma-stimulated HT29-18-N2, and these proliferative responses were efficiently inhibited by the addition of anti-CD86 monoclonal antibody. Costimulatory effect of CD86-expressing colonic epithelial cells isolated from inflamed mucosa of ulcerative colitis was also demonstrated at suboptimal phytohemagglutinin stimulation in CD4(+) T cells.
Colonic epithelial cells may act as antigen-presenting cells, and contribute to the activation of T cells through costimulatory molecule CD86 expression in inflamed colonic mucosa.
共刺激信号对于T细胞活化至关重要。本研究旨在证实共刺激分子CD86和CD80在人结肠上皮细胞中的表达,并评估它们在炎症性结肠黏膜中T细胞活化中的功能作用。
通过结肠黏膜免疫组织化学、逆转录聚合酶链反应以及对分离的结肠上皮细胞和细胞系进行流式细胞术分析,评估CD86和CD80的表达。在亚最佳植物血凝素刺激下,还评估了表达CD86的结肠上皮细胞对纯化的CD4(+) T细胞增殖的共刺激作用。
在溃疡性结肠炎患者正常和炎症黏膜分离的结肠上皮细胞中检测到CD86和CD80信使核糖核酸。结肠上皮细胞的免疫组织化学和流式细胞术分析证实,炎症性结肠黏膜中CD86蛋白的细胞表面表达。干扰素γ刺激后,结肠上皮细胞系HT29-18-N2中CD86蛋白的细胞表面表达增加。纯化的CD4(+) T细胞在亚最佳植物血凝素与干扰素γ刺激的HT29-18-N2共刺激下增殖,添加抗CD86单克隆抗体可有效抑制这些增殖反应。在亚最佳植物血凝素刺激下,也证实了从溃疡性结肠炎炎症黏膜分离的表达CD86的结肠上皮细胞对CD4(+) T细胞的共刺激作用。
结肠上皮细胞可能作为抗原呈递细胞,并通过炎症性结肠黏膜中共刺激分子CD86的表达促进T细胞活化。