Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity
Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity
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DOI：
10.1182/blood-2011-11-392951
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发表时间：
2012-04-19
期刊：
影响因子：
20.3
通讯作者：
Lanier, Lewis L.
中科院分区：
文献类型：
--
作者：
Ndhlovu, Lishomwa C.;Lopez-Verges, Sandra;Lanier, Lewis L.
自然杀伤(NK)细胞是天生的淋巴细胞，在对抗病毒感染和癌症方面发挥着重要作用。这一效应是通过NK细胞表达的抑制和激活受体的复杂马赛克实现的，最终决定了NK细胞反应的大小。T细胞免疫球蛋白和粘蛋白结构域(TIM)-3受体最初被鉴定为T辅助分子1特异性的I型膜蛋白，参与调节T细胞反应。人NK细胞在淋巴细胞中转录TIM-3的量最高。TIM-3蛋白在几乎所有成熟的CD56(Dim)CD16(+)NK细胞上表达，在健康成人外周血和脐带血中的未成熟CD56(Bright)CD16(-)NK细胞亚群中异质性表达。IL-15或IL-12和IL-18体外刺激CD56(Bright)CD16(-)NK细胞后，可诱导CD56(Bright)CD16(-)NK细胞表达Tim-3，提示Tim-3是NK细胞的成熟标志。虽然TIM-3已被用于识别功能障碍的T细胞，但高表达TIM-3的NK细胞在细胞因子产生和细胞毒作用方面完全有反应。然而，当TIM-3与抗体交联时，它会抑制NK细胞介导的细胞毒作用。这些发现表明，当NK细胞遇到表达TIM-3同源配体的靶细胞时，NK细胞的反应可能受到负调控。(血。2012年；119(16)：3734-3743)
Natural killer (NK) cells are innate lymphocytes that play an important role against viral infections and cancer. This effect is achieved through a complex mosaic of inhibitory and activating receptors expressed by NK cells that ultimately determine the magnitude of the NK-cell response. The T-cell immunoglobulin- and mucin domain-containing (Tim)-3 receptor was initially identified as a T-helper 1-specific type I membrane protein involved in regulating T-cell responses. Human NK cells transcribe the highest amounts of Tim-3 among lymphocytes. Tim-3 protein is expressed on essentially all mature CD56(dim)CD16(+) NK cells and is expressed heterogeneously in the immature CD56(bright)CD16(-) NK-cell subset in blood from healthy adults and in cord blood. Tim-3 expression was induced on CD56(bright)CD16(-) NK cells after stimulation with IL-15 or IL-12 and IL-18 in vitro, suggesting that Tim-3 is a maturation marker on NK cells. Whereas Tim-3 has been used to identify dysfunctional T cells, NK cells expressing high amounts of Tim-3 are fully responsive with respect to cytokine production and cytotoxicity. However, when Tim-3 was cross-linked with antibodies it suppressed NK cell-mediated cytotoxicity. These findings suggest that NK-cell responses may be negatively regulated when NK cells encounter target cells expressing cognate ligands of Tim-3. (Blood. 2012;119(16):3734-3743)