Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis
Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis
复制标题
DOI：
10.1172/jci200419836
复制
发表时间：
2004-05-01
影响因子：
15.9
通讯作者：
Strober, W
中科院分区：
文献类型：
--
作者：
Fuss, IJ;Heller, F;Strober, W
虽然克罗恩病（CD）已被明确认定为一种Th1炎症，但其同类炎症性肠病——溃疡性结肠炎（UC）的免疫发病机制仍然不明。在此我们发现，来自UC患者的固有层T（LPT）细胞比对照细胞产生的白细胞介素 - 13（和白细胞介素 - 5）明显更多，而干扰素 - γ很少，然而来自CD患者的类似细胞则产生大量干扰素 - γ和少量白细胞介素 - 13。接着我们表明，用抗CD2/和 - CD28或用表达转染CD1d的B细胞刺激带有NK标记（CD161）的UC LPT细胞会诱导大量白细胞介素 - 13产生。虽然这有力地证明了产生白细胞介素 - 13的细胞是一种自然杀伤T（NKT）细胞，但很明显该细胞不表达大多数NKT细胞所特有的恒定NKT细胞受体，因为结合负载α - 半乳糖神经酰胺的四聚体的细胞没有增加，并且α - 半乳糖神经酰胺没有诱导白细胞介素 - 13分泌。最后，我们表明人类NKT细胞系以及UC CD161⁺ LPT细胞对HT - 29上皮细胞都具有细胞毒性，并且这种细胞毒性因白细胞介素 - 13而增强。这些研究表明，UC与一种由产生白细胞介素 - 13且对上皮细胞具有细胞毒性潜能的非经典NKT细胞介导的非典型Th2反应有关。
While Crohn disease (CD) has been clearly identified as a Th1 inflammation, the immunopathogenesis of its counterpart inflammatory bowel disease, ulcerative colitis (UC), remains enigmatic. Here we show that lamina propria T (LPT) cells from UC patients produce significantly greater amounts of IL-13 (and IL-5) than control cells and little IFN-gamma, whereas comparable cells from CD patients produce large amounts of IFN-gamma and small amounts of IL-13. We then show that stimulation of UC LPT cells bearing an NK marker (CD161) with anti-CD2/ and-CD28 or with B cells expressing transfected CD1d induces substantial IL-13 production. While this provided firm evidence that the IL-13-producing cell is an NK T (NKT) cell, it became clear that this cell does not express invariant NKT cell receptors characteristic of most NKT cells since there was no increase in cells binding alpha-galactosylceramide-loaded tetramers, and alpha-galactosylceramide did not induce IL-13 secretion. Finally, we show that both human NKT cell lines as well as UC CD161(+) LPT cells are cytotoxic for HT-29 epithelial cells and that this cytotoxicity is augmented by IL-13. These studies show that UC is associated with an atypical Th2 response mediated by nonclassical NKT cells producing IL-13 and having cytotoxic potential for epithelial cells.