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T细胞在胸腺发育过程中获得功能性MHC II类/肽复合物以及中枢神经系统定向发病机制。

Acquisition of functional MHC class II/peptide complexes by T cells during thymic development and CNS-directed pathogenesis.

作者信息

Walker Mindi R, Mannie Mark D

机构信息

Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858-4354, USA.

出版信息

Cell Immunol. 2002 Jul-Aug;218(1-2):13-25. doi: 10.1016/s0008-8749(02)00577-4.

Abstract

This study provides evidence that both rat and mouse thymic and splenic T cells express significant levels of MHC class II glycoproteins (MHCII) in vivo. Derivation of rat and mouse chimeras revealed that a major source of MHCII on thymic T cells was acquired from radioresistant host APC. Expression of MHC on thymic T cells appeared physiologically relevant because presentation of rat myelin basic protein (RMBP) by nonadherent, radiosensitive thymic T cells was associated with the adoptive transfer of tolerance. Mature MBP-specific effector T cells isolated from the CNS in both rat and mouse models of EAE also expressed significant levels of MHCII. Adoptive transfer of activated B10.PL MBP/I-A(u)-restricted TCR transgenic T cells into F1(C57BL/6 x B10.PL) mice revealed acquisition of allogeneic I-A(b) on encephalitogenic CNS-derived T cells. Overall, this study indicates that immature and mature T cells in rats and mice acquire functional MHCII in vivo during thymic development and pathogenic inflammation.

摘要

本研究提供了证据,表明大鼠和小鼠的胸腺及脾脏T细胞在体内均表达显著水平的MHC II类糖蛋白(MHCII)。大鼠和小鼠嵌合体的构建显示,胸腺T细胞上MHCII的主要来源是来自辐射抗性宿主抗原呈递细胞(APC)。胸腺T细胞上MHC的表达似乎具有生理相关性,因为非黏附性、辐射敏感的胸腺T细胞呈递大鼠髓鞘碱性蛋白(RMBP)与过继性转移耐受性相关。在大鼠和小鼠实验性自身免疫性脑脊髓炎(EAE)模型中,从中枢神经系统分离出的成熟MBP特异性效应T细胞也表达显著水平的MHCII。将活化的B10.PL MBP/I-A(u)限制性TCR转基因T细胞过继性转移到F1(C57BL/6×B10.PL)小鼠中,结果显示致脑炎的中枢神经系统来源的T细胞获得了同种异体I-A(b)。总体而言,本研究表明,大鼠和小鼠的未成熟和成熟T细胞在胸腺发育和致病性炎症过程中在体内获得功能性MHCII。

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