Fuss I J, Neurath M, Boirivant M, Klein J S, de la Motte C, Strong S A, Fiocchi C, Strober W
Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 1996 Aug 1;157(3):1261-70.
In this study, we investigate whether human inflammatory bowel disease (IBD) (ulcerative colitis and Crohn's disease) is associated with altered lymphokine secretion profiles, as recently found in various animal models of chronic intestinal inflammation. In initial studies, we determined the proliferative responses of purified lamina propria (LP) CD4+ T cells from patients with IBD under defined conditions of T cell stimulation. We found that IBD LP CD4+ T cells in comparison with control LP CD4+ T cells have diminished TCR/CD3 pathway proliferative responses, whereas CD2/CD28 accessory pathway proliferative responses are relatively preserved. In further studies centering on lymphokine production, we showed that LP T cells from inflamed Crohn's disease mucosa manifest increased IFN-gamma secretion compared with control LP T cells, particularly when stimulated via the CD2/CD28 pathway. Subsequent ELISPOT analysis indicated that this was due to an increased number of IFN-gamma-secreting CD4+ T cells. In contrast, IL-4 and IL-5 production by Crohn's disease LP T cells was decreased compared with that of control LP T cells. Of interest, IL-2 production by Crohn's disease LP T cells was also reduced, as was IL-2 production by peripheral blood T cells. In parallel studies, LP T cells from inflamed ulcerative colitis mucosa stimulated via either the TCR/CD3/CD28 or CD2/CD28 produced increased amounts of IL-5, again when measured either as secreted IL-5 or by ELISPOT analysis. Such increased IL-5 production was not associated with increased IL-4 secretion and, in contrast to Crohn's disease, ulcerative colitis LP T cell production of IL-2 and IFN-gamma was normal. Taken together, these studies provide strong evidence that the immunopathologic process characteristic of the two major forms of IBD is associated with very different cytokine secretion patterns. These different patterns may determine the type of inflammatory process present.
在本研究中，我们调查了人类炎症性肠病（IBD）（溃疡性结肠炎和克罗恩病）是否与淋巴因子分泌谱改变有关，这是最近在各种慢性肠道炎症动物模型中发现的情况。在初步研究中，我们测定了在特定T细胞刺激条件下，来自IBD患者的纯化固有层（LP）CD4⁺T细胞的增殖反应。我们发现，与对照LP CD4⁺T细胞相比，IBD LP CD4⁺T细胞的TCR/CD3途径增殖反应减弱，而CD2/CD28辅助途径增殖反应相对保留。在以淋巴因子产生为中心的进一步研究中，我们发现，与对照LP T细胞相比，来自炎症性克罗恩病黏膜的LP T细胞表现出IFN-γ分泌增加，特别是通过CD2/CD28途径刺激时。随后的ELISPOT分析表明，这是由于分泌IFN-γ的CD4⁺T细胞数量增加。相比之下，克罗恩病LP T细胞产生的IL-4和IL-5与对照LP T细胞相比减少。有趣的是，克罗恩病LP T细胞产生的IL-2也减少，外周血T细胞产生的IL-2也是如此。在平行研究中，无论是通过TCR/CD3/CD28还是CD2/CD28刺激，来自炎症性溃疡性结肠炎黏膜的LP T细胞产生的IL-5量增加，同样，无论是以分泌的IL-5还是通过ELISPOT分析来测量。这种IL-5产生增加与IL-4分泌增加无关，与克罗恩病相反，溃疡性结肠炎LP T细胞产生的IL-2和IFN-γ正常。综上所述，这些研究提供了强有力的证据，表明两种主要形式的IBD的免疫病理过程与非常不同的细胞因子分泌模式有关。这些不同的模式可能决定了存在的炎症过程类型。
