TCR sequences and tissue distribution discriminate the subsets of naive and activated/memory Treg cells in mice
TCR sequences and tissue distribution discriminate the subsets of naive and activated/memory Treg cells in mice
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DOI：
10.1002/eji.201445269
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发表时间：
2015-05-01
影响因子：
5.4
通讯作者：
Klatzmann, David
中科院分区：
文献类型：
--
作者：
Bergot, Anne-Sophie;Chaara, Wahiba;Klatzmann, David
对调节性T（Treg）细胞TCR库的分析应有助于阐明其同源抗原的性质和多样性，从而阐明Treg细胞如何保护我们免受自身免疫性疾病的侵害。我们早期鉴定了CD 44（hi）CD 62 L（low）激活/记忆（am）Treg细胞作为具有高周转率和可能的自身特异性的Treg细胞亚群。我们现在报道amTreg细胞主要分布在引流深层组织的淋巴结（LN）中。CDR 3谱分析的多变量分析首先揭示amTreg TCR库不同于初始Treg细胞（nTreg细胞）和效应T（Teff）细胞。此外，在深LN与浅LN中，TCR深度测序进一步揭示了多样化的nTreg细胞和amTreg细胞库，尽管其多样性比Teff细胞少两倍，并且库丰富度在深LN与浅LN Treg细胞中显著较低。重要的是，扩增的克隆型主要在深LN amTreg细胞中检测到，一些占库的20%。引人注目的是，这些克隆型在nTreg细胞中不存在，但在Teff细胞中以低频率发现。我们的研究结果，在非操作小鼠中获得，表明不同的抗原靶向幼稚和amTreg细胞和amTreg细胞是自我特异性的。我们提出的数据是一致的Treg细胞分化的指导性组成部分。
Analyses of the regulatory T (Treg) cell TCR repertoire should help elucidate the nature and diversity of their cognate antigens and thus how Treg cells protect us from autoimmune diseases. We earlier identified CD44(hi)CD62L(low) activated/memory (am) Treg cells as a Treg-cell subset with a high turnover and possible self-specificity. We now report that amTreg cells are predominantly distributed in lymph nodes (LNs) draining deep tissues. Multivariate analyses of CDR3 spectratyping first revealed that amTreg TCR repertoire is different from that of naive Treg cells (nTreg cells) and effector T (Teff) cells. Furthermore, in deep- versus superficial LNs, TCR- deep sequencing further revealed diversified nTreg-cell and amTreg-cell repertoires, although twofold less diverse than that of Teff cells, and with repertoire richness significantly lower in deep-LN versus superficial-LN Treg cells. Importantly, expanded clonotypes were mostly detected in deep-LN amTreg cells, some accounting for 20% of the repertoire. Strikingly, these clonotypes were absent from nTreg cells, but found at low frequency in Teff cells. Our results, obtained in nonmanipulated mice, indicate different antigenic targets for naive and amTreg cells and that amTreg cells are self-specific. The data we present are consistent with an instructive component in Treg-cell differentiation.