Thomas Seddon Y, Hou Runhua, Boyson Jonathan E, Means Terry K, Hess Christoph, Olson Douglas P, Strominger Jack L, Brenner Michael B, Gumperz Jenny E, Wilson S Brian, Luster Andrew D
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, 13th Street, Charlestown, MA 02129, USA.
J Immunol. 2003 Sep 1;171(5):2571-80. doi: 10.4049/jimmunol.171.5.2571.
CD1d-restricted T cells (NKT cells) are innate memory cells activated by lipid Ags and play important roles in the initiation and regulation of the immune response. However, little is known about the trafficking patterns of these cells or the tissue compartment in which they exert their regulatory activity. In this study, we determined the chemokine receptor profile expressed by CD1d-restricted T cells found in the peripheral blood of healthy volunteers as well as CD1d-restricted T cell clones. CD1d-restricted T cells were identified by Abs recognizing the invariant Valpha24 TCR rearrangement or by binding to CD1d-Fc fusion tetramers loaded with alpha-GalCer. CD1d-restricted T cells in the peripheral blood and CD1d-restricted T cell clones expressed high levels of CXCR3, CCR5, and CCR6; intermediate levels of CXCR4 and CXCR6; and low levels of CXCR1, CCR1, CCR2, and CX(3)CR1, a receptor pattern often associated with tissue-infiltrating effector Th1 cells and CD8+ T cells. Very few of these cells expressed the lymphoid-homing receptors CCR7 or CXCR5. CCR4 was expressed predominantly on CD4+, but not on double-negative CD1d-restricted T cells, which may indicate differential trafficking patterns for these two functionally distinct subsets. CD1d-restricted T cell clones responded to chemokine ligands for CXCR1/2, CXCR3, CXCR4, CXCR6, CCR4, and CCR5 in calcium flux and/or chemotaxis assays. These data indicate that CD1d-restricted T cells express a chemokine receptor profile most similar to Th1 inflammatory homing cells and suggest that these cells perform their function in peripheral tissue sites rather than in secondary lymphoid organs.
CD1d限制性T细胞（自然杀伤T细胞）是由脂质抗原激活的固有记忆细胞，在免疫应答的启动和调节中发挥重要作用。然而，关于这些细胞的迁移模式或它们发挥调节活性的组织区室，人们了解甚少。在本研究中，我们确定了健康志愿者外周血中发现的CD1d限制性T细胞以及CD1d限制性T细胞克隆所表达的趋化因子受体谱。通过识别不变的Valpha24 TCR重排的抗体或通过与负载α-GalCer的CD1d-Fc融合四聚体结合来鉴定CD1d限制性T细胞。外周血中的CD1d限制性T细胞和CD1d限制性T细胞克隆表达高水平的CXCR3、CCR5和CCR6；中等水平的CXCR4和CXCR6；以及低水平的CXCR1、CCR1、CCR2和CX(³)CR1，这种受体模式通常与组织浸润效应性Th1细胞和CD8⁺ T细胞相关。这些细胞中很少有表达淋巴细胞归巢受体CCR7或CXCR5的。CCR4主要表达于CD4⁺细胞上，而不在双阴性CD1d限制性T细胞上表达，这可能表明这两个功能不同的亚群具有不同的迁移模式。在钙流和/或趋化性测定中，CD1d限制性T细胞克隆对CXCR1/2、CXCR3、CXCR4、CXCR6、CCR4和CCR5的趋化因子配体有反应。这些数据表明，CD1d限制性T细胞表达的趋化因子受体谱与Th1炎症归巢细胞最为相似，并提示这些细胞在外周组织部位而非二级淋巴器官中发挥其功能。
