Camoglio L, Te Velde A A, Tigges A J, Das P K, Van Deventer S J
Laboratory of Experimental Internal Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands.
Inflamm Bowel Dis. 1998 Nov;4(4):285-90. doi: 10.1002/ibd.3780040406.
Experimental data indicate that mucosal CD4+ T cells play an important role in the pathogenesis of inflammatory bowel disease (IBD). Based on the pattern of cytokine production, CD4+ T cells may be distinguished into two different phenotypes. Th1 responses are characterized by secretion of interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, lymphotoxin, and interferon (IFN)-gamma and are associated with delayed-type hypersensitivity reactions, whereas Th2 responses, which are characterized by secretion of IL-4, IL-5, and IL-10, have been associated with humoral immune responses and allergy. To assess the number of IFN-alpha and IL-4 positive cells in IBD and normal intestinal specimens, frozen sections from intestinal specimens from 10 Crohn's disease (CD), 8 ulcerative colitis (UC), and 8 healthy controls were examined by immunohistochemistry. Monoclonal antibodies for CD3, CD8, IFN-gamma, and IL-4 were used. T-lymphocyte infiltration and cytokine expression by epithelial, lamina propria, and submucosal cells were scored on a four-point scale by two independent observers who were blinded for the clinical data. One-way analysis of variance (ANOVA) testing was used for statistical analysis. In intestinal specimens from IBD patients, the number of CD3+ cells was found increased in the lamina propria and, within the submucosa, this increase was significant (p < 0.001). In CD the number of lamina propria IFN-gamma positive cells was significantly increased as compared with controls (p < 0.002). In UC the number of both IFN-gamma and IL-4 producing cells in the lamina propria was not significantly increased as compared with controls. The present results confirm the existence of a Th1-biased pattern production in CD but not in UC.
实验数据表明，黏膜CD4+ T细胞在炎症性肠病（IBD）的发病机制中起重要作用。根据细胞因子产生模式，CD4+ T细胞可分为两种不同的表型。Th1反应的特征是分泌白细胞介素（IL）-2、肿瘤坏死因子（TNF）-α、淋巴毒素和干扰素（IFN）-γ，并与迟发型超敏反应相关，而以分泌IL-4、IL-5和IL-10为特征的Th2反应则与体液免疫反应和过敏相关。为了评估IBD和正常肠道标本中IFN-α和IL-4阳性细胞的数量，采用免疫组织化学方法检测了10例克罗恩病（CD）、8例溃疡性结肠炎（UC）和8例健康对照者肠道标本的冰冻切片。使用了针对CD3、CD8、IFN-γ和IL-4的单克隆抗体。由两名对临床数据不知情的独立观察者对上皮细胞、固有层和黏膜下层细胞的T淋巴细胞浸润和细胞因子表达进行四分制评分。采用单因素方差分析（ANOVA）进行统计学分析。在IBD患者的肠道标本中，发现固有层中CD3+细胞数量增加，在黏膜下层中这种增加具有显著性（p < 0.001）。与对照组相比，CD患者固有层中IFN-γ阳性细胞数量显著增加（p < 0.002）。与对照组相比，UC患者固有层中产生IFN-γ和IL-4的细胞数量均未显著增加。目前的结果证实CD中存在Th1偏向性产生模式，而UC中不存在。
