A primary role for human central memory cells in tissue immunosurveillance
A primary role for human central memory cells in tissue immunosurveillance
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DOI：
10.1182/bloodadvances.2017011346
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发表时间：
2018-02-13
期刊：
影响因子：
7.5
通讯作者：
Clark, Rachael A.
中科院分区：
文献类型：
--
作者：
Gehad, Ahmed;Teague, Jessica E.;Clark, Rachael A.
中央记忆T细胞（T-CM）巡逻淋巴结，提供针对已知病原体的中央免疫监视，但尚未被描述为进行主要组织免疫监视。我们分析了来自相同供体的人T-CM与效应记忆T细胞（T-EM）中组织归巢地址素的表达。在人体中，大多数人T-CM对皮肤或肠道具有嗜性，T-CM的总体组织嗜性与T-EM相当。T-CM存在于健康、非炎症的人皮肤、肺、结肠和宫颈中，表明T-CM在外周组织的初级免疫监视中起作用。T-CM也具有有效的效应子功能; 80%的CD 8（+）T-CM产生TC 1/TC 2/TC 17/TC 22细胞因子。T-CM注射到人皮肤移植小鼠中迁移到皮肤中，并诱导与TEM注射小鼠相当的炎性皮疹。总之，人T-CM表达外周组织归巢受体，其水平与其效应记忆对应物相似，存在于健康人体组织中，具有令人印象深刻的效应功能，并且可以单独作用以诱导人移植小鼠的皮肤炎症。我们的研究支持了一种新的作用，人类T-CM在外周组织的初级免疫监视，并强调了这种长寿的细胞类型在组织免疫反应中的重要作用。
Central memory T cells (T-CM) patrol lymph nodes, providing central immunosurveillance against known pathogens, but have not been described as conducting primary tissue immunosurveillance. We analyzed the expression of tissue-homing addressins in human T-CM vs effector memory T cells (T-EM) from the same donors. In humans, the majority of human T-CM were tropic for either skin or gut, and the overall tissue tropism of T-CM was comparable to that of T-EM. T-CM were present in healthy, noninflamed human skin, lung, colon, and cervix, suggesting a role for T-CM in the primary immunosurveillance of peripheral tissues. T-CM also had potent effector functions; 80% of CD8(+) T-CM produced TC1/TC2/TC17/TC22 cytokines. T-CM injected into human skin-grafted mice migrated into skin and induced inflammatory eruptions comparable to TEM-injected mice. In summary, human T-CM express peripheral tissue-homing receptors at levels similar to their effector memory counterparts, are found in healthy human tissues, have impressive effector functions, and can act alone to induce skin inflammation in human engrafted mice. Our studies support a novel role for human T-CM in primary immunosurveillance of peripheral tissues and highlight the important role of this long-lived cell type in tissue-based immune responses.