The expansion and selection of T cell receptor alpha beta intestinal intraepithelial T cell clones
The expansion and selection of T cell receptor alpha beta intestinal intraepithelial T cell clones
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DOI：
10.1002/eji.1830260429
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发表时间：
1996-04-01
影响因子：
5.4
通讯作者：
Kourilsky, P
中科院分区：
文献类型：
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作者：
Regnault, A;Levraud, JP;Kourilsky, P
在常规小鼠中，肠上皮内淋巴细胞（IEL）的T细胞受体（TCR）α β（-）CD 8 α α（+）和CD 8 α β（-）亚群构成两个亚群。每一个包含几百个克隆，其表达在个体遗传上相同的小鼠中不同的明显随机的受体库（Regnault，A.，Cumano，A.，Vassalli，P.，Guy-Grand，D.和Kourilsky，P.，J. Exp. Med. 1994.一百八十：我们分析了来自个体无菌小鼠小肠的分选的CD 8 α α和CD 8 α β TCR α β（-）IEL群体的库多样性，所述个体无菌小鼠含有比常规小鼠少十倍的TCR α β（+）T细胞。无菌成年小鼠的CD 8 α α和CD 8 α β IEL群体的TCR β库显示与常规小鼠相同程度的寡克隆性。这些结果表明，肠道微生物菌群不是TCR α β（+）IEL的所有寡克隆性的原因。微生物区系的存在导致独立于细菌的克隆的扩增。为了评估IEL克隆在常规小鼠中的扩增程度，我们继续通过定量PCR在成年动物的小肠的总部分和相邻部分中测量其体内克隆大小。我们发现，CD 8 α α和CD 8 α β TCR α β IEL克隆具有异质性大小模式，克隆含有3 × 10（3）个细胞至1.2 × 10（6）个细胞，克隆在个体小鼠中定性和定量不同。来自给定IEL克隆的细胞在整个小肠的长度上不是均匀分布的。观察到TCR α β IEL群体包含数百个大小和分布非常不均匀的克隆，这表明它们来自有限数量的前体，这些前体可以缓慢但连续地更新，并在上皮中经历广泛的克隆扩增。
In conventional mice, the T cell receptor (TCR)alpha beta(-) CD8 alpha alpha(+) and CD8 alpha beta(-) subsets of the intestinal intraepithelial lymphocytes (IEL) constitute two subpopulations. Each comprise a few hundred clones expressing apparently random receptor repertoires which are different in individual genetically identical mice (Regnault, A., Cumano, A., Vassalli, P., Guy-Grand, D. and Kourilsky, P., J. Exp. Med. 1994. 180: 1345).We analyzed the repertoire diversity of sorted CD8 alpha alpha and CD8 alpha beta TCR alpha beta(-) IEL populations from the small intestine of individual germ-free mice that contain ten times less TCR alpha beta(+) T cells than conventional mice. The TCR beta repertoire of the CD8 alpha alpha and the CD8 alpha beta IEL populations of germ-free adult mice shows the same degree of oligoclonality as that of conventional mice. These results show that the intestinal microflora is not responsible for the repertoire oligoclonality of TCR alpha beta(+) IEL. The presence of the microflora leads to an expansion of clones which arise independently of bacteria. To evaluate the degree of expansion of IEL clones in conventional mice, we went on to measure their clone sizes in vivo by quantitative PCR in the total and in adjacent sections of the small intestine of adult animals. We found that both the CD8 alpha alpha and the CD8 alpha beta TCR alpha beta IEL clones have a heterogeneous size pattern, with clones containing from 3 x 10(3) cells up to 1.2 x 10(6) cells, the clones being qualitatively and quantitatively different in individual mice. Cells from a given IEL clone are not evenly distributed throughout the length of the small intestine. The observation that the TCR alpha beta IEL populations comprise a few hundred clones of very heterogeneous size and distribution suggests that they arise from a limited number of precursors, which may be slowly but continuously renewed, and undergo extensive clonal expansion in the epithelium.