Transendothelial migratory pathways of Vδ1+TCRγδ+ and Vδ2+TCRγδ+ T lymphocytes from healthy donors and multiple sclerosis patients:: Involvement of phosphatidylinositol 3 kinase and calcium calmodulin-dependent kinase II
Transendothelial migratory pathways of Vδ1+TCRγδ+ and Vδ2+TCRγδ+ T lymphocytes from healthy donors and multiple sclerosis patients:: Involvement of phosphatidylinositol 3 kinase and calcium calmodulin-dependent kinase II
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DOI：
10.4049/jimmunol.168.12.6071
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发表时间：
2002-06-15
影响因子：
4.4
通讯作者：
Battistini, L
中科院分区：
文献类型：
--
作者：
Poggi, A;Zocchi, MR;Battistini, L
We have previously reported that the Vdelta2(+)TCRgammadelta(+) T lymphocyte subset, expressing the NK receptor protein 1a (NKRP1a; CD161), is expanded in patients with relapsing-remitting multiple sclerosis and uses this molecule to migrate through endothelium. In this work, we show that Vdelta1(+) and Vdelta2(+) gammadelta T lymphocytes use distinct signal transduction pathways to accomplish this function. Indeed, we have found that Vdelta1(+) cells lack NKRP1a and selectively express the platelet endothelial cell adhesion molecule 1 (PECAM1; CD31), which drives transendothelial migration of this cell subset, at variance with Vdelta2(+) T cells, which are PECAM1 negative and use NKRP1a for transmigration. Interestingly, when Vdelta2(+) T cells were pretreated with two specific inhibitors of the calcium calmodulin-dependent kinase II KN62 and KN93, but not with the inactive compound KN92, the number of migrating cells and the rate of transmigration were significantly decreased. In turn, the phosphatidylinositol 3 kinase blockers wortmannin and LY294002 exerted a dose-dependent inhibition of Vdelta1(+) cell migration. Finally, NKRP1a and PECAM1 engagement led to activation of different signal transduction pathways: indeed, oligomerization of NKRP1a on Vdelta2(+) T cells activates calcium calmodulin-dependent kinase II, while occupancy of PECAM1 on Vdelta1(+) cells triggers the phosphatidylinositol 3 kinase-dependent Akt/protein kinase Balpha activation. These findings suggest that subsets of gammadelta T lymphocytes may migrate to the site of lesion in multiple sclerosis using two different signaling pathways to extravasate.
