TCR repertoire dynamics in the pancreatic lymph nodes of non-obese diabetic (NOD) mice at the time of disease initiation
TCR repertoire dynamics in the pancreatic lymph nodes of non-obese diabetic (NOD) mice at the time of disease initiation
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DOI：
10.1016/j.molimm.2008.03.009
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发表时间：
2008-06-01
影响因子：
3.6
通讯作者：
Hoglund, Petter
中科院分区：
文献类型：
--
作者：
Berglund, Jelena Petrovc;Mariotti-Ferrandiz, Encarnita;Hoglund, Petter
小鼠T细胞发育在出生时未完成，并在生命的第一个月内继续，此时T细胞从胸腺中排出并定殖于次级造血器官以建立外周T细胞库。在相同的时间段内，在非肥胖糖尿病（NOD）小鼠的胰腺淋巴结（PLN）中启动针对β细胞衍生的自身抗原的T细胞应答。我们假设T细胞发育和T细胞活化对组织特异性抗原的联合作用将在NOD小鼠的两个不同淋巴结站中产生独特的TCR库。为了验证这一假设，我们测定了10、14、18和22日龄NOD雌性PLN和腹股沟淋巴结（ILN）中TCR的第三互补决定区（CDR 3）的长度分布。对所有BV基因的分析显示，在第10天和第22天之间，所有基因组发生了显著的扰动，但PLN和ILN基因组之间没有统计学差异。相反，当使用BJ特异性引物扩增一组BV链时，与ILN相比，在PLN中观察到几种独特的TCR扰动。我们建议，在外周淋巴结的NOD小鼠的TCR库动态发展之间的10和22天的年龄作为一个发展过程的结果。在这种发展的基础上，局部环境可能会微调该库，可能是通过局部APC呈递的组织特异性抗原刺激T细胞。(C)2008爱思唯尔有限公司保留所有权利。
Mouse T-cell development is unfinished at birth and continues during the first month of life, when T cells exit from the thymus and colonize secondary hematopoietic organs to build up a peripheral T-cell repertoire. T-cell responses against beta-cell-derived autoantigens are initiated in the pancreatic lymph nodes (PLN) of non-obese diabetic (NOD) mice during the same time period. We hypothesized that the combined effect of T-cell development and T-cell activation against tissue-specific antigens would create unique TCR repertoires in two different lymph node stations in NOD mice. To test this hypothesis, we determined the length distribution of the third complementarity-determining region (CDR3) of the TCR in the PLN and the inguinal lymph nodes (ILN) of 10, 14,18 and 22-day-old NOD females. The analysis of all the BV genes revealed significant perturbations of the repertoire between days 10 and 22 but with no statistical differences between the PLN and ILN repertoires. In contrast, when a set of BV chains were amplified using BJ-specific primers, several unique TCR perturbations were observed in the PLN compared to the ILN. We propose that the TCR repertoire in peripheral lymph nodes of NOD mice develops dynamically between 10 and 22 days of age as a result of a developmental process. On top of that development, the local environment may fine-tune that repertoire, possibly by means of stimulation of T cells by tissue-specific antigens presented by local APC. (C) 2008 Elsevier Ltd. All rights reserved.