Common clonal origin of central and resident memory T cells following skin immunization.
Common clonal origin of central and resident memory T cells following skin immunization.
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DOI：
10.1038/nm.3860
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发表时间：
2015-06
期刊：
影响因子：
82.9
通讯作者：
Kupper TS
中科院分区：
文献类型：
--
作者：
Gaide O;Emerson RO;Jiang X;Gulati N;Nizza S;Desmarais C;Robins H;Krueger JG;Clark RA;Kupper TS
淋巴组织中的中央记忆T细胞和周围组织中的驻留记忆T细胞在保护性免疫中起着不同的作用。两者都是在原发感染后产生的，但TRM和中医细胞的克隆起源尚不清楚。为了解决这个问题，用蛋白质抗原、化学半抗原或非复制型痘病毒对小鼠进行皮肤免疫。然后，我们利用编码T细胞受体基因β链CDR3区的高通量测序技术分析了来自不同组织的抗原激活的T细胞，以同时跟踪数以千计的独特T细胞。对于皮肤中产生的每一个丰富的TRM克隆，在淋巴结(LN)中都存在一个携带相同TCR的丰富的中医克隆。因此，在皮肤免疫后，抗原反应性皮肤TRM和LN中医克隆来自共同的初始T细胞前体，产生重叠的TCR谱系。尽管它们具有相同的TCR，但TRM介导小鼠的快速接触超敏反应(CHS)，而中药则介导延迟和减弱的反应。对人体的研究证实了过敏性接触性皮炎中皮肤TRM的产生。因此，通过皮肤免疫可以从相同的幼稚T细胞同时产生类似数量的皮肤TRM和LN Tcm。
Central memory T (TCM) cells in lymph nodes (LN) and resident memory T (TRM) cells in peripheral tissues play distinct roles in protective immunity. Both are generated after primary infections, but the clonal origin of TRM and TCM cells is unclear. To address this question, mice were immunized through the skin with either a protein antigen, a chemical hapten, or a non-replicating poxvirus. We then analyzed antigen activated T cells from different tissues using high-throughput sequencing (HTS) of the gene (Tcrbv) encoding T cell receptor gene β chain CDR3 region to simultaneously track thousands of unique T cells. For every abundant TRM clone generated in the skin, an abundant TCM clone bearing the identical TCR was present in lymph nodes (LN). Thus antigen reactive skin TRM and LN TCM clones were derived from a common naive T cell precursor after skin immunization, generating overlapping TCR repertoires. Although they bore the same TCR, TRM mediated rapid contact hypersensitivity (CHS) responses in mice, whereas TCM mediated delayed and attenuated responses. Studies in human subjects confirmed the generation of skin TRM in allergic contact dermatitis. Thus, immunization through skin simultaneously generates skin TRM and LN TCM in similar numbers from the same naïve T cells.