Molecular biology of extrathymic T cells for the development of mucosal inflammation

IL-10是粘膜免疫系统中的重要调节细胞因子，如IL-10缺陷的小鼠自发地发展克罗恩病样结肠炎的事实所支持的。Th 1驱动的CD 4 ^+ T细胞对肠道细菌的异常应答似乎在小鼠结肠炎的发病机制中起重要作用。然而，目前还没有鉴定出特定的细菌或细菌产物，结肠炎是否是由识别特定肽-MHC复合物的CD 4 ^+ T细胞活化介导的仍存在争议。在本研究中，我们利用免疫显微镜技术分析了从IL-10缺陷小鼠中分离的结肠CD 4 ^+ T细胞的TCRβ链CDR 3长度谱型。对白细胞介素-10缺陷小鼠进行筛选后，在TCR Vβ 13和结肠CD 4 ^+ T细胞的14个亚家族中发现了一个限制性克隆型。相反，在外周淋巴组织的CD 4 ^+ T细胞中，单个TCR Vβ亚群的克隆型呈高斯分布。虽然个人 ...更多信息 在拉霍亚和大坂饲养的其他IL-10缺陷小鼠中也注意到疾病相关应答的变异性，可能是由于疾病的不同阶段、遗传背景或饲养环境，结肠炎相关的公共克隆似乎在所有测试的患病小鼠中共享。为了确定是否涉及公共克隆，我们测定了克隆的DNA序列。来自不同背景的白细胞介素-10缺陷性结肠炎小鼠的结肠CD 4 ^+ T细胞具有相同的公共基序。常见的基序是SXDWG和SATGNYAEQ。这些基序在患病小鼠的外周淋巴组织以及未患病小鼠的结肠中未观察到。因此，共同基序可能与一种公共肠道来源的抗原有关，这可能对IBD模型中致病性CD 4 ^+ T细胞的发育很重要。在个体小鼠中，Vβ-Jβ使用的选择可能是随机的;然而，通过重组机制的SXDWG基序的表观遗传产生和在肠道环境中对该基序的选择可能对触发IBD很重要。少

IL-10 is an important regulatory cytokine in the mucosal immune system, as supported by the fact that mice deficient in IL-10 spontaneously develop Crohn's disease-like colitis. An aberrant, Th1-driven CD4^+ T-cell response to enteric bacteria seems to be important in the pathogenesis of this murine colitis. However, no specific bacteria or bacterial products have been identified, whether the colitis is mediated by the activation of CD4^+ T cells that recognize specific peptide-MHC complexes is controversial. In this study, we analyzed the TCRβ chain CDR3 length spectratype of colonic CD4^+ T cells isolated from diseased IL-10-deficient mice by using the Immunoscope technique. Screening of the diseased interleukin-10 deficient mice resulted in a restricted clonotype in TCR Vβ 13 and 14 subfamilies of colonic CD4^+ T cells. In contrast, a Gaussian distribution of clonotype of individual TCR Vβ subsets was observed in CD4^+ T cells from the peripheral lymphoid tissues. Although individua … More l variability in the disease-related response was also noted in other IL-10-deficient mice maintained in La Jolla and Osaka, perhaps because of different stages of the disease, genetic background, or the housing environment, colitis-related public clones seemed to be shared in all the tested diseased mice. To address whether public clones were involved, we determined DNA sequence of the clones. Public motifs were shared in colonic CD4^+ T cells from different background interleukin-10 deficient mice with colitis. The frequently found motifs were SXDWG and SATGNYAEQ. These motifs were not seen in the peripheral lymphoid tissues of diseased mice as well as the colon of nondiseased mice. Thus, the common motif may be related to a public gut-derived antigen, which could be important for the development of pathogenic CD4^+ T cells in this IBD model. The selection of Vβ-Jβ usage is perhaps stochastic in individual mice ; however, the epigenetic generation of SXDWG motif by the recombination machinery and selection for this motif in the gut environment could be : important for triggering IBD. Less