Holtmeier Wolfgang, Käller Judith, Geisel Wiebke, Pabst Reinhard, Caspary Wolfgang F, Rothkötter Hermann J
Medizinische Klinik II, Division of Gastroenterology, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
J Immunol. 2002 Aug 15;169(4):1993-2002. doi: 10.4049/jimmunol.169.4.1993.
gammadelta T cells are an important component of the mucosal immune system. Previously, we have shown that the TCR delta repertoire in human intestine is polyclonal at birth and becomes increasingly restricted with age. In this study, we expand those studies to the pig which allows more extensive experiments including several organs. Tissues from different mucosal sites like the stomach, duodenum, ileum, Peyer's patches, jejunum, and colon, and also extraintestinal sites like the lung, spleen, thymus and mesenteric lymph nodes, were obtained from conventionally reared pigs aged 2 wk to 5.5 years. In addition, tissues were also obtained from 10-wk-old specified pathogen- and germ-free pigs. TCRDV1-DV5 transcripts were amplified by RT-PCR after which complementarity-determining region 3 spectratyping was performed. Individual bands were excised from the gels and directly sequenced. The intestinal TCR delta repertoire showed increasing restriction with age and was highly oligoclonal in the adult 2- to 5.5-year-old pigs. In old pigs, we observed a striking compartmentalization. Different TCR delta repertoires were present between the lungs and the intestinal mucosa but also within different parts of the gastrointestinal tract. However, occasionally we observed identical TCR delta transcripts in the intestine and the lungs and shared clones could be detected also along the entire gastrointestinal tract. Thus, subsets of gammadelta T cells are likely to transport immunological information between different compartments of the immune system. Furthermore, these data support the hypothesis that in each mucosal site, different Ags are responsible for selecting and maintaining the gammadelta TCR over time.
γδT细胞是黏膜免疫系统的重要组成部分。此前,我们已经表明,人类肠道中的TCRδ库在出生时是多克隆的,并且随着年龄的增长变得越来越受限。在本研究中,我们将这些研究扩展到猪,这使得我们能够进行更广泛的实验,包括对多个器官的研究。从2周龄至5.5岁的常规饲养猪中获取来自不同黏膜部位(如胃、十二指肠、回肠、派尔集合淋巴结、空肠和结肠)以及肠外部位(如肺、脾、胸腺和肠系膜淋巴结)的组织。此外,还从10周龄的无特定病原体和无菌猪中获取组织。通过RT-PCR扩增TCRDV1-DV5转录本,然后进行互补决定区3光谱分型。从凝胶中切下各个条带并直接测序。肠道TCRδ库显示出随着年龄增长而增加的受限性,并且在2至5.5岁的成年猪中高度寡克隆。在老年猪中,我们观察到了明显的分区化。肺和肠黏膜之间以及胃肠道的不同部分之间存在不同的TCRδ库。然而,我们偶尔会在肠道和肺中观察到相同的TCRδ转录本,并且在整个胃肠道中也可以检测到共享的克隆。因此,γδT细胞亚群可能在免疫系统的不同部分之间传递免疫信息。此外,这些数据支持以下假设:在每个黏膜部位,随着时间的推移,不同的抗原负责选择和维持γδTCR。