Trafficking machinery of NKT cells:: shared and differential chemokine receptor expression among Vα24+Vβ11+ NKT cell subsets with distinct cytokine-producing capacity
Trafficking machinery of NKT cells:: shared and differential chemokine receptor expression among Vα24+Vβ11+ NKT cell subsets with distinct cytokine-producing capacity
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DOI：
10.1182/blood-2001-12-0196
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发表时间：
2002-07-01
期刊：
影响因子：
20.3
通讯作者：
Butcher, EC
中科院分区：
文献类型：
--
作者：
Kim, CH;Johnston, B;Butcher, EC
自然杀伤T细胞（NKT）是免疫系统的重要调节因子，但其运输机制，包括趋化因子受体的表达，一直没有明确的定义。与其他传统t细胞群体不同，我们发现大多数NKT细胞表达淋巴外组织或炎症相关趋化因子受体（CCR2、CCR5和CXCR3），而少数NKT细胞表达淋巴组织归巢趋化因子受体（CCR7和CXCR5）。具有淋巴结归巢潜力的群体（L选择素（+）CCR7(+)）仅存在于CD4 NKT细胞的一小部分中。我们发现趋化因子受体在NKT细胞亚群中的表达存在差异：CCR4主要由高细胞因子（白细胞介素-4/白细胞介素-2）产生（CD4）的NKT亚群表达，而CCR1、CCR6和CXCR6则优先由低细胞因子产生的CD8和CD4(-)CD8（-）亚群表达。与此一致，TARC/CCL17（一种CCR4配体）诱导CD4 NKT亚群的优先趋化，而LARC/CCL20（一种CCR6配体）和MIP-1alpha/CCL3（一种CCR1配体）的趋化活性主要集中在CD8和CD4(-)CD8(-) NKT细胞。我们得出结论，与传统的幼稚T细胞、记忆T细胞或效应T细胞不同，整个NKT细胞群表达非淋巴组织归巢趋化因子受体，然而NKT细胞亚群通过显示一些趋化因子受体的不同和相互表达模式而彼此差异很大。我们的研究结果确定了趋化因子受体，这些受体对人类血液NKT细胞亚群的运输可能很重要，并揭示了它们的功能（细胞因子生产能力）依赖于不同的运输潜力。
Natural killer T (NKT) cells are important regulators of the immune system, but their trafficking machinery, including expression of chemokine receptors, has been poorly defined. Unlike other conventional T-cell populations, we show that most NKT cells express receptors for extralymphoid tissue or inflammation-related chemokines (CCR2, CCR5, and CXCR3), while few NKT cells express lymphoid tissue-homing chemokine receptors (CCR7 and CXCR5). A population with homing potential for lymph nodes (L selectin(+) CCR7(+)) exists only within a small subset of CD4 NKT cells. We show differential expression of chemokine receptors among NKT cell subsets: CCR4 is mainly expressed by a high cytokine (interieukin-4/interleukin-2)-producing (CD4) NKT subset, while CCR1, CCR6, and CXCR6 are preferentially expressed by the low cytokine-producing CD8 and CD4(-)CD8(-) subsets. In line with this, TARC/CCL17 (a CCR4 ligand) induces preferential chemotaxis of the CD4 NKT subset, while chemotactic activities of LARC/CCL20(a CCR6 ligand) and MIP-1alpha/CCL3 (a CCR1 ligand) are focused on the CD8 and CD4(-)CD8(-) NKT cells. We conclude that, unlike conventional naive, memory, or effector T cells, the entire NKT cell population expresses nonlymphoid tissue homing chemokine receptors, yet NKT cell subsets differ considerably from each other by displaying distinct and reciprocal expression patterns of some chemokine receptors. Our results identify chemokine receptors that are potentially important for trafficking of human blood NKT cell subsets and reveal their function (cytokine production capacity)-dependent differential trafficking potentials.