Shiobara N, Suzuki Y, Aoki H, Gotoh A, Fujii Y, Hamada Y, Suzuki S, Fukui N, Kurane I, Itoh T, Suzuki R
Department of Rheumatology and Clinical Immunology, Clinical Research Center for Allergy and Rheumatology, National Sagamihara Hospital, Kanagawa, Japan.
Clin Exp Immunol. 2007 Oct;150(1):13-21. doi: 10.1111/j.1365-2249.2007.03443.x. Epub 2007 Jul 5.
Ulcerative colitis (UC) is a chronic relapsing-remitting inflammatory bowel disease (IBD) that affects the colon and the rectum producing debilitating symptoms, which impair ability to function and quality of life. The aetiology of IBD is incompletely understood, but within the lymphocyte population, specific T cell subsets are known to be major factors in the development of intestinal immune pathology while different subsets are essential regulators, controlling IBD. Hence, IBD is thought to reflect dysregulated T cell behaviour. This study was to investigate if the normal molecular configuration of the T cell receptor (TCR) repertoire is compromised in patients with UC. The percentage of T cell-bearing beta-chain 4 (TCRBV4) was high in patients with UC, and T cells showed polyclonal expansion in the presence of bacterial superantigens (SA) such as streptococcal mitogenic exotoxin Z-2 (SMEZ-2), indicating that bacterial SA promote specific TCRBV family expansion. Further, in patients with UC, the duration of UC was significantly longer in patients with skewed TCRBV4 compared with patients without TCRBV4 skewing, suggesting that long-term exposure to bacterial SA such as SMEZ-2 might promote systemic immune disorders like the remission-relapsing cycles seen in patients with UC. In conclusion, our observations in this study support the perception that the systemic activation of T cells by enteric bacterial SA might lead to a dysregulated, but exuberant immune activity causing the remission and flare-up cycle of mucosal inflammation in patients with UC. Future studies should strengthen our findings and increase understanding on the aetiology of IBD.
溃疡性结肠炎（UC）是一种慢性复发-缓解型炎症性肠病（IBD），会影响结肠和直肠，产生使人虚弱的症状，损害功能能力和生活质量。IBD的病因尚未完全明确，但在淋巴细胞群体中，特定的T细胞亚群已知是肠道免疫病理发展的主要因素，而不同的亚群是控制IBD的重要调节因子。因此，IBD被认为反映了T细胞行为失调。本研究旨在调查UC患者的T细胞受体（TCR）库的正常分子构型是否受到损害。UC患者中携带β链4的T细胞（TCRBV4）百分比很高，并且T细胞在存在细菌超抗原（SA）如链球菌促有丝分裂外毒素Z-2（SMEZ-2）的情况下显示出多克隆扩增，这表明细菌SA促进特定TCRBV家族的扩增。此外，在UC患者中，TCRBV4偏斜的患者与无TCRBV4偏斜的患者相比，UC病程明显更长，这表明长期暴露于如SMEZ-2这样的细菌SA可能会促进全身免疫紊乱，就像UC患者出现的缓解-复发周期一样。总之，我们在本研究中的观察结果支持这样一种观点，即肠道细菌SA对T细胞的全身激活可能导致失调但旺盛的免疫活动，从而引起UC患者黏膜炎症的缓解和发作周期。未来的研究应加强我们的发现，并增进对IBD病因的理解。
