Johnston Brent, Kim Chang H, Soler Dulce, Emoto Masashi, Butcher Eugene C
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
J Immunol. 2003 Sep 15;171(6):2960-9. doi: 10.4049/jimmunol.171.6.2960.
NKT cells play important roles in the regulation of diverse immune responses. Therefore, chemokine receptor expression and chemotactic responses of murine TCRalphabeta NKT cells were examined to define their homing potential. Most NKT cells stained for the chemokine receptor CXCR3, while >90% of Valpha14i-positive and approximately 50% of Valpha14i-negative NKT cells expressed CXCR6 via an enhanced green fluorescent protein reporter construct. CXCR4 expression was higher on Valpha14i-negative than Valpha14i-positive NKT cells. In spleen only, subsets of Valpha14i-positive and -negative NKT cells also expressed CXCR5. NKT cell subsets migrated in response to ligands for the inflammatory chemokine receptors CXCR3 (monokine induced by IFN-gamma/CXC ligand (CXCL)9) and CXCR6 (CXCL16), and regulatory chemokine receptors CCR7 (secondary lymphoid-tissue chemokine (SLC)/CC ligand (CCL)21), CXCR4 (stromal cell-derived factor-1/CXCL12), and CXCR5 (B cell-attracting chemokine-1/CXCL13); but not to ligands for other chemokine receptors. Two NKT cell subsets migrated in response to the lymphoid homing chemokine SLC/CCL21: CD4(-) Valpha14i-negative NKT cells that were L-selectin(high) and enriched for expression of Ly49G2 (consistent with the phenotype of most NKT cells found in peripheral lymph nodes); and immature Valpha14i-positive cells lacking NK1.1 and L-selectin. Mature NK1.1(+) Valpha14i-positive NKT cells did not migrate to SLC/CCL21. BCA-1/CXCL13, which mediates homing to B cell zones, elicited migration of Valpha14i-positive and -negative NKT cells in the spleen. These cells were primarily CD4(+) or CD4(-)CD8(-) and were enriched for Ly49C/I, but not Ly49G2. Low levels of chemotaxis to CXCL16 were only detected in Valpha14i-positive NKT cell subsets. Our results identify subsets of NKT cells with distinct homing and localization patterns, suggesting that these populations play specialized roles in immunological processes in vivo.
NKT细胞在多种免疫反应的调节中发挥着重要作用。因此，我们检测了小鼠TCRαβ NKT细胞的趋化因子受体表达和趋化反应，以确定它们的归巢潜能。大多数NKT细胞表达趋化因子受体CXCR3，而通过增强型绿色荧光蛋白报告构建体，超过90%的Vα14i阳性和大约50%的Vα14i阴性NKT细胞表达CXCR6。Vα14i阴性NKT细胞上的CXCR4表达高于Vα14i阳性NKT细胞。仅在脾脏中，Vα14i阳性和阴性NKT细胞亚群也表达CXCR5。NKT细胞亚群对炎症趋化因子受体CXCR3（IFN-γ诱导的单核因子/CXC配体（CXCL）9）和CXCR6（CXCL16）以及调节性趋化因子受体CCR7（二级淋巴组织趋化因子（SLC）/CC配体（CCL）21）、CXCR4（基质细胞衍生因子-1/CXCL12）和CXCR5（B细胞吸引趋化因子-1/CXCL13）的配体产生迁移反应；但对其他趋化因子受体的配体没有反应。两个NKT细胞亚群对淋巴归巢趋化因子SLC/CCL21产生迁移反应：L-选择素（高）且富含Ly49G2表达的CD4（-）Vα14i阴性NKT细胞（与外周淋巴结中发现的大多数NKT细胞的表型一致）；以及缺乏NK1.1和L-选择素的未成熟Vα14i阳性细胞。成熟的NK1.1（+）Vα14i阳性NKT细胞不会迁移到SLC/CCL21。介导归巢到B细胞区的BCA-1/CXCL13引发了脾脏中Vα14i阳性和阴性NKT细胞的迁移。这些细胞主要是CD4（+）或CD4（-）CD8（-），且富含Ly49C/I，但不富含Ly49G2。仅在Vα14i阳性NKT细胞亚群中检测到对CXCL16的低水平趋化性。我们的结果确定了具有不同归巢和定位模式的NKT细胞亚群，表明这些群体在体内免疫过程中发挥着特殊作用。
