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用成熟的胸腺来源T细胞重建的SCID小鼠肠道黏膜淋巴细胞的生成

Generation of intestinal mucosal lymphocytes in SCID mice reconstituted with mature, thymus-derived T cells.

作者信息

Camerini V, Sydora B C, Aranda R, Nguyen C, MacLean C, McBride W H, Kronenberg M

机构信息

Department of Pediatrics, University of Virginia, Charlottesville 22908, USA.

出版信息

J Immunol. 1998 Mar 15;160(6):2608-18.

PMID:9510158
Abstract

Transfer of peripheral lymph node lymphocytes to SCID mice leads to the long term establishment of mucosal T lymphocytes within the epithelium and lamina propria of the small and large intestines. Analysis of engrafted intraepithelial lymphocytes (IEL) showed that they had acquired a surface phenotype that in several respects is typical of IEL. In addition, the functional profile of engrafted IEL derived from lymph node T cells was similar to that of normal IEL; as the donor-derived T cells exhibited a strong cytolytic activity, a poor proliferative response to mitogenic stimuli, and a tendency to home and expand specifically in the intestine upon transfer to secondary SCID recipients. Optimal engraftment of intestinal T cells required bacterial flora, as the number of lymphocytes was greatly reduced in SCID recipients with a reduced flora. These results demonstrate that mature, thymus-derived T cells can migrate to the intestine and become functionally specialized to the intestinal milieu. The acquisition of phenotypic markers characteristic of the intestinal microenvironment by engrafted cells suggests that T cell migration of lymphocytes to the SCID intestine is not aberrant, but it may reflect processes that are ongoing in immunocompetent mice. Furthermore, these data suggest that the homing and/or expansion of typical, thymus-derived T cells in the intestine may be driven by luminal Ags such as those derived from bacterial flora.

摘要

将外周淋巴结淋巴细胞转移至重症联合免疫缺陷(SCID)小鼠体内,可导致小肠和大肠上皮及固有层中长期存在黏膜T淋巴细胞。对移植的上皮内淋巴细胞(IEL)进行分析表明,它们获得了在多个方面具有IEL典型特征的表面表型。此外,源自淋巴结T细胞的移植IEL的功能特征与正常IEL相似;因为供体来源的T细胞表现出强大的细胞溶解活性、对有丝分裂原刺激的增殖反应较差,并且在转移至二级SCID受体后有在肠道中特异性归巢和扩增的倾向。肠道T细胞的最佳移植需要细菌菌群,因为菌群减少的SCID受体中的淋巴细胞数量会大幅减少。这些结果表明,成熟的、源自胸腺的T细胞可以迁移至肠道,并在功能上适应肠道环境。移植细胞获得肠道微环境特有的表型标志物表明,淋巴细胞向SCID肠道的T细胞迁移并非异常,而是可能反映了免疫健全小鼠中正在进行的过程。此外,这些数据表明,典型的、源自胸腺的T细胞在肠道中的归巢和/或扩增可能由腔内抗原驱动,例如源自细菌菌群的抗原。

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