Development and compartmentalization of the porcine TCR δ repertoire at mucosal and extraintestinal sites:: The pig as a model for analyzing the effects of age and microbial factors
Development and compartmentalization of the porcine TCR δ repertoire at mucosal and extraintestinal sites:: The pig as a model for analyzing the effects of age and microbial factors
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DOI：
10.4049/jimmunol.169.4.1993
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发表时间：
2002-08-15
影响因子：
4.4
通讯作者：
Rothkötter, HJ
中科院分区：
文献类型：
--
作者：
Holtmeier, W;Käller, J;Rothkötter, HJ
Gammadelta T细胞是黏膜免疫系统的重要组成部分。此前，我们已经证明，人类肠道中的TCR Delta谱系在出生时是多克隆的，并随着年龄的增长而变得越来越有限。在这项研究中，我们将这些研究扩展到猪身上，允许进行更广泛的实验，包括几个器官。取自胃、十二指肠、回肠、Peyer‘s补片、空肠和结肠等不同粘膜部位以及肺、脾、胸腺和肠系膜淋巴结等肠外部位的组织，取自2~5.5周龄的常规饲养猪。此外，还从10周龄的特定病原体和无菌猪身上获得了组织。RT-PCR扩增TCRDV1-DV5转录本，然后进行互补决定区3分型。从凝胶中切下单独的条带并直接测序。肠道TCR增量谱随年龄增长而增加，在2~5.5岁成年猪中呈高度寡克隆性。在老猪身上，我们观察到了一种惊人的区隔。不同的TCR5谱系存在于肺和肠粘膜之间，也存在于胃肠道的不同部分。然而，我们偶尔在肠和肺中观察到相同的TCR5转录本，整个胃肠道也可以检测到共享克隆。因此，Gammadelta T细胞的亚群可能在免疫系统的不同部分之间传输免疫信息。此外，这些数据支持这样的假设，即在每个粘膜部位，不同的AGs负责随着时间的推移选择和维持Gammadelta TCR。
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 5 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 5 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.