Selective expansion of specific T cell receptors in the inflamed colon of Crohn's disease.
Selective expansion of specific T cell receptors in the inflamed colon of Crohn's disease.
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克罗恩病发炎结肠中特定 T 细胞受体的选择性扩增。
DOI：
10.1172/jci118921
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Silver,J
中科院分区：
文献类型：
--
作者：
Gulwani-Akolkar,B;Akolkar,PN;Minassian,A;Pergolizzi,R;McKinley,M;Mullin,G;Fisher,S;Silver,J
为明确克罗恩病(CD)患者的疾病特异性T细胞变化，采用定量聚合酶链式反应和DNA序列分析，比较了7例CD患者结肠炎性和非活动期固有层淋巴细胞(LPL)的T细胞受体BV谱。从同一个体的疾病活动性部分和非活动性部分分离的LPL的BV谱有很大的不同。此外，几乎所有的差异都发生在CD4+LPL中，CD8+LPL中的差异很小。尽管疾病活跃组织相对于疾病非活跃组织增加的BV片段在所有七个CD患者中的模式不同，但在所有七个人的疾病活跃组织中都有几个BV片段均匀增加。对这些BV片段的CDR3长度分析和DNA测序显示，在7名CD患者中，有6名患者存在显著程度的寡克隆，而同一人的非疾病活动组织中没有这种情况。这些观察表明，CD中至少有一部分炎症是由CD4+T细胞对特定抗原做出反应的结果。这种炎症特异性的CD4+T细胞的分离可能使我们有可能确定CD中负责炎症过程的抗原，并为更好地了解其发病机制提供依据。
To identify disease-specific T cell changes that occur in Crohn's disease (CD), the T cell receptor BV repertoires of lamina propria lymphocytes (LPL) isolated from both the inflamed and "disease-inactive" colons of seven CD patients were compared by the quantitative PCR and DNA sequence analysis. It was observed that the BV repertoires of LPL isolated from the disease-active and disease-inactive parts of the colon from the same individual were very different. Furthermore, nearly all of the differences occurred in CD4+ LPL, with very few differences in the CD8+ population of LPL. Although the pattern of BV segments that was increased in disease-active tissue relative to disease-inactive tissue was different for all seven CD patients, there were several BV segments that increased uniformly in the disease-active tissue of all seven individuals. CDR3 length analysis and DNA sequencing of these BV segments revealed that in six of the seven CD patients there was a striking degree of oligoclonality that was absent from disease-inactive tissue of the same individual. These observations suggest that at least some of the inflammation in CD is the result of responses by CD4+ T cells to specific antigens. The isolation of such inflammation-specific CD4+ T cells may make it possible to identify the antigens that are responsible for the inflammatory process in CD and provide a better understanding of its pathogenesis.