Shimamoto Masaru, Ueno Yoshitaka, Tanaka Shinji, Onitake Toshiko, Hanaoka Rie, Yoshioka Kyoko, Hatakeyama Tsuyoshi, Chayama Kazuaki
Department of Medicine and Molecular Science, Hiroshima University, Hiroshima 734-8551, Japan.
World J Gastroenterol. 2007 Dec 7;13(45):5995-6002. doi: 10.3748/wjg.v13.45.5995.
To investigate the role of local colonic mucosal NK receptor-positive T (NKR(+) T) cells in the regulation of intestinal inflammation, we analyzed the population and function of these cells in ulcerative colitis (UC).
Colonic mucosal tissues were obtained from colonoscopic biopsies of the descending colon from 96 patients with UC (51 endoscopically uninflamed, 45 inflamed) and 18 normal controls. Endoscopic appearance and histologic score at the biopsied site were determined by Matts' classification. A single cell suspension was prepared from each biopsy by collagenase digestion. Two NKR(+) T cell subsets, CD56(+) (CD56(+)CD3(+)) T cells and CD161(+) (CD161(+)CD3(+)) T cells, were detected by flow cytometric analysis. Intracellular cytokine analysis for anti-inflammatory cytokine interleukin-10 (IL-10) was performed by in vitro stimulation with phorbol-myristate-acetate (PMA) and ionomycin.
CD56(+) T cells and CD161(+) T cells are present in the normal human colon and account for 6.7% and 21.3% of all mononuclear cells, respectively. The populations of both CD56(+) T cells and CD161(+) T cells were decreased significantly in the inflamed mucosa of UC. In contrast, the frequency of conventional T cells (CD56(-)CD3(+) cells and CD161(-)CD3(+) cells) was similar among the patient and control groups. The populations of NKR(+) T cells were correlated inversely with the severity of inflammation, which was classified according to the endoscopic and histologic Matts' criteria. Interestingly, approximately 4% of mucosal NKR(+) T cells expressing IL-10 were detected by in vitro stimulation with PMA and ionomycin.
Selective reduction in the population of colonic mucosal NKR(+) T cells may contribute to the development of intestinal inflammation in UC.
为了研究局部结肠黏膜自然杀伤受体阳性T（NKR(+)T）细胞在肠道炎症调节中的作用，我们分析了这些细胞在溃疡性结肠炎（UC）中的数量和功能。
从96例UC患者（51例内镜检查无炎症，45例有炎症）和18例正常对照者的降结肠结肠镜活检中获取结肠黏膜组织。活检部位的内镜表现和组织学评分采用马茨分类法确定。通过胶原酶消化从每个活检组织制备单细胞悬液。通过流式细胞术分析检测两个NKR(+)T细胞亚群，即CD56(+)（CD56(+)CD3(+)）T细胞和CD161(+)（CD161(+)CD3(+)）T细胞。通过佛波酯-肉豆蔻酸酯-乙酸酯（PMA）和离子霉素体外刺激进行抗炎细胞因子白细胞介素-10（IL-10）的细胞内细胞因子分析。
CD56(+)T细胞和CD161(+)T细胞存在于正常人体结肠中，分别占所有单核细胞的6.7%和21.3%。UC炎症黏膜中CD56(+)T细胞和CD161(+)T细胞的数量均显著减少。相比之下，患者组和对照组中常规T细胞（CD56(-)CD3(+)细胞和CD161(-)CD3(+)细胞）的频率相似。NKR(+)T细胞的数量与根据内镜和组织学马茨标准分类的炎症严重程度呈负相关。有趣的是，通过PMA和离子霉素体外刺激检测到约4%的黏膜NKR(+)T细胞表达IL-10。
结肠黏膜NKR(+)T细胞数量的选择性减少可能有助于UC中肠道炎症的发展。
