Barcode clonal tracking of tissue-resident immune cells in rhesus macaque highlights distinct clonal distribution pattern of tissue NK cells.
Barcode clonal tracking of tissue-resident immune cells in rhesus macaque highlights distinct clonal distribution pattern of tissue NK cells.
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条形码克隆追踪猕猴体内的组织驻留免疫细胞，突出了组织中NK细胞的独特克隆分布模式。
DOI：
10.3389/fimmu.2022.994498
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发表时间：
2022
影响因子：
7.3
通讯作者：
Dunbar, Cynthia E.
中科院分区：
文献类型：
--
作者：
Wu, Chuanfeng;Liang, Jialiu A.;Brenchley, Jason M.;Shin, Taehoon;Fan, Xing;Mortlock, Ryland D.;Abraham, Diana M.;Allan, David S. J.;Thomas, Marvin L.;Hong, So Gun;Dunbar, Cynthia E.
组织驻留（TR）免疫细胞在促进组织稳态、协调针对感染和肿瘤的免疫应答以及维持免疫记忆方面发挥重要作用。虽然研究表明这些细胞在表型和功能上与外周血（PB）中发现的细胞不同，但尚未在灵长类动物或人类中全面研究这些组织群体之间的克隆关系。我们利用含有高多样性条形码的恒河猴造血干细胞和祖细胞的自体移植来追踪T、B、骨髓和自然杀伤（NK）细胞群体在组织（包括肝、脾、肺和胃肠道（GI））中的克隆分布，与移植后的PB纵向比较，特别地，我们集中于不含内源性克隆标志物且先前未在此背景下研究的NK细胞。T细胞表现出组织特异性克隆扩增，如预期的那样，既与血液T细胞重叠又与之不同。相反，B细胞和髓系细胞在各种组织和血液中显示出更加同质的克隆模式。TR NK的克隆分布在个体动物之间具有更大的异质性。在一些动物中，正如我们先前报道的，我们观察到成熟的CD 56-CD 16 + NK细胞中的大PB克隆扩增。值得注意的是，我们在CD 16-CD 56-（DN）NK亚群中发现了一组单独的高度扩增的PB克隆，其也有助于检查的所有组织中的TR NK细胞，在TR CD 56-CD 16+和DN群体两者中，但在分析的所有组织中在CD 56 +16- TR NK中不存在。此外，我们观察到对单个组织（如肺或胃肠道）特异性的TR NK克隆组和在肝脏和脾脏中共享的TR NK克隆组，与其他组织不同。结合先前的功能数据表明NK记忆仅限于肝脏或其他TR NK细胞，这些克隆扩增的TR NK细胞可能对未来NK细胞组织免疫记忆的研究感兴趣，并对基于NK的免疫疗法的开发和对NK记忆的理解产生影响。
Tissue resident (TR) immune cells play important roles in facilitating tissue homeostasis, coordinating immune responses against infections and tumors, and maintaining immunological memory. While studies have shown these cells are distinct phenotypically and functionally from cells found in the peripheral blood (PB), the clonal relationship between these populations across tissues has not been comprehensively studied in primates or humans. We utilized autologous transplantation of rhesus macaque hematopoietic stem and progenitor cells containing high diversity barcodes to track the clonal distribution of T, B, myeloid and natural killer (NK) cell populations across tissues, including liver, spleen, lung, and gastrointestinal (GI) tract, in comparison with PB longitudinally post-transplantation, in particular we focused on NK cells which do not contain endogenous clonal markers and have not been previously studied in this context. T cells demonstrated tissue-specific clonal expansions as expected, both overlapping and distinct from blood T cells. In contrast, B and myeloid cells showed a much more homogeneous clonal pattern across various tissues and the blood. The clonal distribution of TR NK was more heterogenous between individual animals. In some animals, as we have previously reported, we observed large PB clonal expansions in mature CD56-CD16+ NK cells. Notably, we found a separate set of highly expanded PB clones in CD16-CD56- (DN) NK subset that were also contributing to TR NK cells in all tissues examined, both in TR CD56-CD16+ and DN populations but absent in CD56+16- TR NK across all tissues analyzed. Additionally, we observed sets of TR NK clones specific to individual tissues such as lung or GI tract and sets of TR NK clones shared across liver and spleen, distinct from other tissues. Combined with prior functional data that suggests NK memory is restricted to liver or other TR NK cells, these clonally expanded TR NK cells may be of interest for future investigation into NK cell tissue immunological memory, with implications for development of NK based immunotherapies and an understanding of NK memory.
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