Intestinal γδ T cells develop in mice lacking thymus, all lymph nodes, Peyer's patches, and isolated lymphoid follicles
Intestinal γδ T cells develop in mice lacking thymus, all lymph nodes, Peyer's patches, and isolated lymphoid follicles
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DOI：
10.4049/jimmunol.174.4.1906
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发表时间：
2005-02-15
影响因子：
4.4
通讯作者：
Ishikawa, H
中科院分区：
文献类型：
--
作者：
Nonaka, S;Naito, T;Ishikawa, H
通过对携带GFP基因而不是RAG-2产物的裸鼠的分析，最近有报道称，在缺乏胸腺生成的情况下，肠系膜淋巴结和Peyer‘s Patches(PP)而不是肠道隐窝是成熟T细胞(如胸腺非依赖性肠上皮内T细胞(IEL))的关键发源地。为了探索和评估这一重要问题，我们通过将淋巴毒素-β受体-Ig和肿瘤坏死因子受体55-Ig融合蛋白注射到与雄性nu/nu小鼠交配的定时妊娠nu/+小鼠(nu/nu LNP-小鼠)中，产生了缺乏所有淋巴结(LN)和PP的nu/nu小鼠。我们还产生了nu/nu Aly/ay(Aly，淋巴发育不良)双突变小鼠，这些小鼠天生就缺乏所有的LN、PP和分离的淋巴滤泡。虽然Gammadelta-IEL的数量略少于nu/nu小鼠，但在nu/nu LNP-和nu/nu Aly/Aly小鼠的肠道上皮细胞中发现了大量的Gammadelta-1EL定植。值得注意的是，CD8αα(+)Gammadelta-IEL亚集的种群规模保持不变，这些Gammadelta-IEL对TCR-Gamma链可变基因片段的使用没有改变，这些nu/nu LNP-和nu/nu Aly/Aly小鼠的密码配对的发育保持不变。这些发现表明，所有的LN，包括肠系膜LN、PP和分离的淋巴滤泡，并不是裸鼠发生Gammadelta-IEL的绝对必要条件。
Through analysis of athymic (nu/nu) mice carrying a transgenic gene encoding GFP instead of RAG-2 product, it has recently been reported that, in the absence of thymopoiesis, mesenterie lymph nodes and Peyer's patches (PP) but not gut cryptopatches are pivotal birthplace of mature T cells such as the thymus-independent intestinal intraepithelial T cells (IEL). To explore and evaluate this important issue, we generated nu/nu mice lacking all lymph nodes (LN) and PP by administration of lymphotoxin-beta receptor-Ig and TNF receptor 55-Ig fusion proteins into the timed pregnant nu/+ mice that had been mated with male nu/nu mice (nu/nu LNP- mice). We also generated nu/nu aly/ay (aly, alymphoplasia) double-mutant mice that inherently lacked all LN, PP, and isolated lymphoid follicles. Although gammadelta-IEL were slightly smaller in number than those in nu/nu mice, substantial colonization of gammadelta-1EL was found to take place in the intestinal epithelia of nu/nu LNP- and nu/nu aly/aly mice. Notably, the population size of a major CD8alphaalpha(+) gammadelta-IEL subset was maintained, the use of TCR-gamma-chain variable gene segments by these gammadelta-IEL was unaltered, and the development of cryptopatches remained intact in these nu/nu LNP- and nu/nu aly/aly mice. These findings indicate that all LN, including mesenteric LN, PP, and isolated lymphoid follicles, are not an absolute requirement for the development of gammadelta-IEL in athymic nu/nu mice.