Shibahara Takeshi, Miyazaki Kaori, Sato Daisuke, Matsui Hirohumi, Yanaka Akinori, Nakahara Akira, Tanaka Naomi
Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan.
J Gastroenterol. 2005 Sep;40(9):878-86. doi: 10.1007/s00535-005-1631-y.
Intimate cross-talk may take place between intestinal epithelial cells and intraepithelial lymphocytes (IEL). The purpose of this study was to analyze the influence of lymphocyte migration into the epithelium on epithelial function, using an in vitro "IEL homing" model.
Molecular expression on epithelial cells was analyzed by flow cytometry. The barrier function of the epithelial monolayer was assessed by transepithelial electrical resistance. Cytokine production was measured by enzyme-linked immunosorbent assay (ELISA).
(1) IEL homing into the epithelia induced significant phenotypic changes in epithelial cells; upregulation of MHC class I, and II, intercellular adhesion molecule (ICAM)-1, and CD44. IEL-derived interferon-gamma (IFN-gamma) could partially account for this alteration, as a neutralizing antibody (Ab) against IFN-gamma inhibited the upregulation of these molecules, except for CD44. (2) A marked fall in transepithelial electrical resistance was observed 4 h after IEL homing started, and Ab against IFN-gamma slightly inhibited this fall in resistance. (3) The production of interleukin (IL)-8 and IFN-gamma inducible protein-10 (IP-10), but not transforming growth factor (TGF)-beta1 or tumor necrosis factor (TNF)-alpha, in the epithelial monolayer was markedly induced after IEL homing in a basolaterally polarized fashion. IEL-conditioned media also induced the production of these cytokines in epithelial cells, thus suggesting that IEL-derived soluble factor(s) induce epithelial chemokine production.
Under inflammatory conditions, IEL obviously interact with epithelial cells and upregulate adhesion molecules, alter barrier function, and enhance chemokine production. Because such alterations may increase epithelial permeability to luminal antigens or accelerate the migration of other inflammatory cells, our results suggest that IEL have a critical role in mucosal immunity.
肠道上皮细胞与上皮内淋巴细胞（IEL）之间可能存在密切的相互作用。本研究旨在利用体外“ IEL归巢”模型分析淋巴细胞迁移至上皮细胞对上皮功能的影响。
通过流式细胞术分析上皮细胞上的分子表达。采用跨上皮电阻评估上皮单层的屏障功能。通过酶联免疫吸附测定（ELISA）测量细胞因子的产生。
（1）IEL归巢至上皮细胞可诱导上皮细胞发生显著的表型变化；主要组织相容性复合体（MHC）I类和II类、细胞间黏附分子（ICAM）-1和CD44上调。IEL衍生的γ干扰素（IFN-γ）可部分解释这种变化，因为抗IFN-γ中和抗体可抑制这些分子（CD44除外）的上调。（2）IEL归巢开始4小时后，观察到跨上皮电阻显著下降，抗IFN-γ抗体可轻微抑制这种电阻下降。（3）IEL归巢以基底外侧极化方式进行后，上皮单层中白细胞介素（IL）-8和IFN-γ诱导蛋白10（IP-10）的产生明显增加，但转化生长因子（TGF）-β1或肿瘤坏死因子（TNF）-α无明显变化。IEL条件培养基也可诱导上皮细胞产生这些细胞因子，因此提示IEL衍生的可溶性因子可诱导上皮趋化因子的产生。
在炎症条件下，IEL明显与上皮细胞相互作用，上调黏附分子，改变屏障功能，并增强趋化因子的产生。由于这些改变可能增加上皮细胞对腔内抗原的通透性或加速其他炎症细胞的迁移，我们的结果提示IEL在黏膜免疫中起关键作用。
