The abundant NK cells in human secondary lymphoid tissues require activation to express killer cell Ig-like receptors and become cytolytic
The abundant NK cells in human secondary lymphoid tissues require activation to express killer cell Ig-like receptors and become cytolytic
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DOI：
10.4049/jimmunol.172.3.1455
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发表时间：
2004-02-01
影响因子：
4.4
通讯作者：
Münz, C
中科院分区：
文献类型：
--
作者：
Ferlazzo, G;Thomas, D;Münz, C
自然杀伤细胞是先天免疫中重要的细胞溶解细胞。我们已经鉴定了脾脏、淋巴结和扁桃体的人类NK细胞。超过95%的外周血NK细胞和85%的脾脏NK细胞是CD56(dim)CD16(+)，表达穿孔素、天然细胞毒性受体（ncr） NKp30和NKp46，以及部分杀伤细胞igg样受体（KIRs）。相比之下，淋巴结中的NK细胞主要是CD56（亮）CD16（-）表型，缺乏穿孔素。此外，它们缺乏KIRs和所有NCR的表达，除了低水平的NKp46。扁桃体NK细胞也缺乏穿孔素、KIRs、NKp30和CD16，但部分表达NKp44和NKp46。然而，在IL-2刺激下，淋巴结和扁桃体NK细胞上调NCRs，表达穿孔素，并获得对NK敏感靶细胞的细胞溶解活性。此外，它们在IL-2激活后表达CD16和KIRs，因此表现出与外周血NK细胞相似的表型。我们假设IL-2可以调动次生淋巴组织的NK细胞介导免疫应答过程中的自然杀伤。由于人类淋巴细胞中淋巴结占40%，外周血仅占2%，淋巴结和相关组织中新发现的穿孔素（-）NK细胞室的数量可能超过穿孔素（+）NK细胞。这些结果也提示次级淋巴器官可能是NK细胞分化和自我耐受性获得的部位。
Natural killer cells are important cytolytic cells in innate immunity. We have characterized human NK cells of spleen, lymph nodes, and tonsils. More than 95% of peripheral blood and 85% of spleen NK cells are CD56(dim)CD16(+) and express perforin, the natural cytotoxicity receptors (NCRs) NKp30 and NKp46, as well as in part killer cell Ig-like receptors (KIRs). In contrast, NK cells in lymph nodes have mainly a CD56(bright)CD16(-) phenotype and lack perforin. In addition, they lack KIRs and all NCR expression, except low levels of NKp46. The NK cells of tonsils also lack perforin, KIRs, NKp30, and CD16, but partially express NKp44 and NKp46. Upon IL-2 stimulation, however, lymph node and tonsilar NK cells up-regulate NCRs, express perforin, and acquire cytolytic activity for NK-sensitive target cells. In addition, they express CD16 and KIRs upon IL-2 activation, and therefore display a phenotype similar to peripheral blood NK cells. We hypothesize that IL-2 can mobilize the NK cells of secondary lymphoid tissues to mediate natural killing during immune responses. Because lymph nodes harbor 40% and peripheral blood only 2% of all lymphocytes in humans, this newly characterized perforin(-) NK cell compartment in lymph nodes and related tissues probably outnumbers perforin(+) NK cells. These results also suggest secondary lymphoid organs as a possible site of NK cell differentiation and self-tolerance acquisition.