Factors that influence the thymic selection of CD8αα intraepithelial lymphocytes.

Factors that influence the thymic selection of CD8αα intraepithelial lymphocytes.
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影响 CD8αα 上皮内淋巴细胞胸腺选择的因素。

DOI:
10.1038/s41385-020-0295-5
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发表时间:
2021-01
期刊:
影响因子:
8
通讯作者:
Robey, Ellen A.
Robey, Ellen A.
中科院分区:
医学1区
文献类型:
--
作者:
Kurd, Nadia S.;Hoover, Ashley;Yoon, Jaewon;Weist, Brian M.;Lutes, Lydia;Chan, Shiao Wei;Robey, Ellen A.

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携带对自身肽-MHC复合物具有高亲和力的αβ T细胞受体(TCRαβ)的胸腺细胞经历负选择或转向交替的T细胞谱系,该过程称为激动剂选择。在携带限制于MHC I类的TCR的胸腺细胞中,激动剂选择可导致可归巢至肠道并产生表达CD 8 αα的上皮内淋巴细胞(CD 8 αα IEL)的前体细胞的发育。影响阴性选择与CD 8 αα IEL发展之间选择的因素在很大程度上仍然未知。使用同时支持阴性选择和CD 8 αα IEL形成的同步胸腺组织切片模型,我们表明CD 8 αα IEL形成的亲和力阈值高于阴性选择。我们还研究了肽呈递细胞和细胞因子的影响,以及与这些替代细胞命运相关的迁移模式。我们的数据突出了TCR亲和力和胸腺微环境对T细胞命运的作用。
Thymocytes bearing αβ T cell receptors (TCRαβ) with high affinity for self-peptide-MHC complexes undergo negative selection or are diverted to alternate T cell lineages, a process termed agonist selection. Among thymocytes bearing TCRs restricted to MHC class I, agonist selection can lead to the development of precursors that can home to the gut and give rise to CD8αα-expressing intraepithelial lymphocytes (CD8αα IELs). The factors that influence the choice between negative selection versus CD8αα IEL development remain largely unknown. Using a synchronized thymic tissue slice model that supports both negative selection and CD8αα IEL development, we show that the affinity threshold for CD8αα IEL development is higher than for negative selection. We also investigate the impact of peptide presenting cells and cytokines, and the migration patterns associated with these alternative cell fates. Our data highlight the roles of TCR affinity and the thymic microenvironments on T cell fate.
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