Differential usage of VLA-4 and CXCR4 by CD3+CD56+ NKT cells and CD56+CD16+ NK cells regulates their interaction with endothelial cells
Differential usage of VLA-4 and CXCR4 by CD3+CD56+ NKT cells and CD56+CD16+ NK cells regulates their interaction with endothelial cells
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DOI：
10.1002/eji.200324718
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发表时间：
2004-05-01
影响因子：
5.4
通讯作者：
Peled, A
中科院分区：
文献类型：
--
作者：
Franitza, S;Grabovsky, V;Peled, A
调节 NKT 细胞在 BM 中优先积累的机制尚不清楚。 BM 内皮组成型表达选择素、整合素配体 VCAM-1 和 ICAM-1 以及趋化因子 CXCL12。 NK 和 NKT 细胞亚群在 P-选择素和 E-选择素上都表现出相似的束缚和滚动相互作用，并表达相似水平的整合素、VLA-4 和 LFA-1。尽管 NKT 细胞比 NK 细胞表达更高水平的 CXCR4，但 CXCL1 2（CXCR4 的配体）会快速刺激 NK 和 NKT 细胞与 VCAM-1 和 ICAM-1 的相似水平的粘附。在这两个亚群中，VCAM-1 的停滞依赖于高亲和力 VLA-4，并且这些细胞归巢至 NOD/SCID 的 BM 是 VLA-4 依赖性的。然而，与 NK 细胞的情况相反，CXCL1 2 在剪切流下优先触发 VCAM-1 的滚动和 NKT 细胞的跨内皮迁移。此外，YT NK 细胞系上高水平 CXCR4 的过度表达使它们能够响应 CXCL12 进行迁移。因此，这项研究表明 CXCR4 的表达水平和 VLA-4 在调节 BM 中 NKT 细胞的积累中发挥着重要作用。
The mechanism that regulates the preferential accumulation of NKT cells in the BM is unknown. The BM endothelium constitutively expresses selectins, the integrin ligands VCAM-1 and ICAM-1, and the chemokine CXCL12. Both NK and NKT subsets of cells exhibited similar tethering and rolling interactions on both P-selectin and E-selectin and expressed similar levels of the integrins, VLA-4 and LFA-1. Although NKT cells express higher levels of CXCR4 than NK cells, CXCL1 2 (the ligand for CXCR4) rapidly stimulates similar levels of adhesion of NK and NKT cells to VCAM-1 and ICAM-1. In both subsets, the arrest on VCAM-1 was dependent on high affinity VLA-4 and the homing of these cells to the BM of NOD/SCID was VLA-4-dependent. However, as opposed to the situation for NK cells, CXCL1 2 preferentially triggers, under shear flow, the rolling on VCAM-1 and transendothelial migration of NKT cells. Moreover, over-expression of high levels of CXCR4 on the YT NK cell line enables them to migrate in response to CXCL12. This study therefore suggests an important role for CXCR4 levels of expression and for VLA-4 in regulating the accumulation of NKT cells in the BM.