Duchmann R, Kaiser I, Hermann E, Mayet W, Ewe K, Meyer zum Büschenfelde K H
First Department of Medicine, University of Mainz, Germany.
Clin Exp Immunol. 1995 Dec;102(3):448-55. doi: 10.1111/j.1365-2249.1995.tb03836.x.
Hyporesponsiveness to a universe of bacterial and dietary antigens from the gut lumen is a hallmark of the intestinal immune system. Since hyperresponsiveness against these antigens might be associated with inflammation, we studied the immune response to the indigenous intestinal microflora in peripheral blood, inflamed and non-inflamed human intestine. Lamina propria monocuclear cells (LPMC) isolated from inflamed intestine but not peripheral blood mononuclear cells (PBMC) of IBD patients with active inflammatory disease strongly proliferated after co-culture with sonicates of bacteria from autologous intestine (BsA). Proliferation was inhibitable by anti-MHC class II MoAb, suggesting that it was driven by antigen. LPMC from adjacent non-inflamed intestinal areas of the same IBD patients and PBMC or LPMC isolated from non-inflamed intestine of controls and patients with IBD in remission, in contrast, did not proliferate. PBMC or LPMC which had been tolerant to bacteria from autologous intestine, however, strongly proliferated after co-culture with bacterial sonicates from heterologous intestine (BsH). This proliferation was associated with an expansion of CD8+ T cells, increased expression of activation markers on both CD4+ and CD8+ lymphocyte subsets, and production of IL-12, interferon-gamma (IFN-gamma), and IL-10 protein. These results show that tolerance selectively exists to intestinal flora from autologous but not heterologous intestine, and that tolerance is broken in intestinal inflammation. This may be an important mechanism for the perpetuation of chronic IBD.
对来自肠腔的大量细菌和饮食抗原反应低下是肠道免疫系统的一个标志。由于对这些抗原的高反应性可能与炎症相关，我们研究了外周血、发炎和未发炎的人体肠道对肠道内源性微生物群的免疫反应。与来自自身肠道的细菌超声裂解物（BsA）共培养后，从发炎肠道分离的固有层单核细胞（LPMC）而非患有活动性炎症疾病的IBD患者的外周血单核细胞（PBMC）强烈增殖。增殖可被抗MHC II类单克隆抗体抑制，提示其由抗原驱动。相比之下，来自同一IBD患者相邻未发炎肠道区域的LPMC以及从对照和缓解期IBD患者的未发炎肠道分离的PBMC或LPMC不增殖。然而，对来自自身肠道细菌产生耐受的PBMC或LPMC与来自异源肠道的细菌超声裂解物（BsH）共培养后强烈增殖。这种增殖与CD8 + T细胞的扩增、CD4 +和CD8 +淋巴细胞亚群上激活标志物表达的增加以及IL - 12、干扰素 - γ（IFN - γ）和IL - 10蛋白的产生有关。这些结果表明，对来自自身而非异源肠道的肠道菌群选择性存在耐受，且在肠道炎症中耐受被打破。这可能是慢性IBD持续存在的一个重要机制。
