首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Selective endothelial binding of interleukin-2-dependent human T-cell lines derived from different tissues.
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Selective endothelial binding of interleukin-2-dependent human T-cell lines derived from different tissues.

机译:来自不同组织的白介素2依赖性人T细胞系的选择性内皮结合。

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摘要

The ability of lymphocytes to recognize and bind to high endothelial venules (HEVs) is essential for lymphocyte migration from the blood into lymphoid tissues and into sites of inflammation. Endothelial cell binding capacity also critically determines the clinical usefulness of T-cell lines and clones in immunotherapy. In the present study, interleukin-2-dependent T-cell lines were derived from the blood, lamina propria of the gut, inflamed synovium, synovial fluid, and peripheral lymph nodes. After 3-8 weeks of culture, the expression of homing-associated molecules and binding to mucosal, synovial, and peripheral lymph node HEVs were analyzed. Cell lines derived from the blood and mucosal sites bound significantly better to mucosal and synovial HEVs than to peripheral lymph node HEVs. Three out of seven synovial T-cell lines showed preferential binding to synovial HEVs, whereas the rest bound almost equally well to synovial and mucosal HEVs. T-cell lines from peripheral lymph nodes bound preferentially to lymph node HEVs despite the lack of L-selectin (the peripheral lymph node homing receptor). Expression of the known homing-associated molecules did not predict the HEV-binding specificity of these lines. Importantly, two cell lines bound well to synovial venules, but poorly, if at all, to mucosal or peripheral lymph node HEVs, supporting the concept that synovial-specific HEV recognition mechanisms exist. In conclusion, the tissue origin of T-cell lines critically determines their selectivity for endothelial cell recognition, and besides the known "homing receptors," other molecules may also mediate tissue-specific HEV-binding of interleukin-2-activated T cells.
机译:淋巴细胞识别并结合高内皮小静脉(HEV)的能力对于淋巴细胞从血液向淋巴组织以及炎症部位的迁移至关重要。内皮细胞结合能力还决定了T细胞系和克隆在免疫治疗中的临床实用性。在本研究中,白细胞介素2依赖性T细胞系来源于血液,肠固有层,滑膜发炎,滑液和外周淋巴结。培养3-8周后,分析了归巢相关分子的表达以及与黏膜,滑膜和外周淋巴结HEV的结合。源自血液和粘膜部位的细胞系与粘膜和滑膜HEV的结合明显优于外周淋巴结HEV。 7个滑膜T细胞系中有3个显示出与滑膜HEV的优先结合,而其余的与滑膜和粘膜HEV的结合几乎相同。尽管缺乏L-选择蛋白(外周淋巴结归巢受体),来自外周淋巴结的T细胞系仍优先结合淋巴结HEV。已知的归巢相关分子的表达不能预测这些系的HEV结合特异性。重要的是,两个细胞系与滑膜小静脉结合良好,但与粘膜或外周淋巴结HEV的结合非常弱,即使有的话也很弱,这支持了滑膜特异性HEV识别机制存在的概念。总之,T细胞系的组织起源决定性地决定了它们对内皮细胞识别的选择性,除了已知的“归巢受体”外,其他分子还可以介导白介素2激活的T细胞的组织特异性HEV结合。

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