Selective diapedesis of Th1 cells induced by endothelial cell RANTES.
Selective diapedesis of Th1 cells induced by endothelial cell RANTES.
复制标题
DOI：
10.4049/jimmunol.163.6.3269
复制
发表时间：
1999-09
影响因子：
4.4
通讯作者：
T. Kawai;M. Seki;K. Hiromatsu;J. Eastcott;G. Watts;M. Sugai;D. Smith;S. Porcelli;M. Taubman
中科院分区：
文献类型：
--
作者：
T. Kawai;M. Seki;K. Hiromatsu;J. Eastcott;G. Watts;M. Sugai;D. Smith;S. Porcelli;M. Taubman
分化的 CD4 T 细胞根据其产生的细胞因子可分为 Th1 和 Th2 类型。 Th1 型或 Th2 型细胞上趋化因子受体的差异表达表明 Th1 型和 Th2 型细胞不仅在细胞因子产生方面存在差异，而且在迁移能力方面也存在差异。在跨内皮迁移测定中，用 IFN-γ 刺激内皮细胞选择性增强 Th1 型细胞的迁移，但不增强 Th2 型细胞的迁移。 Th1型细胞的增强的迁移依赖于内皮细胞产生的趋化因子RANTES，如中和RANTES的Ab或其受体CCR5的Ab抑制迁移的发现所表明的。中和趋化因子巨噬细胞炎症蛋白 1α 或单核细胞趋化蛋白 1 的抗体不会抑制 Th1 选择性迁移。抗CD18和抗CD54阻断Th1型细胞与内皮细胞粘附的基础水平并且还抑制迁移，而抗RANTES仅阻断迁移，表明RANTES似乎诱导粘附T细胞的迁移。 RANTES 似乎通过对磷酸肌醇 3-激酶抑制剂渥曼青霉素和 Rho GTP 结合蛋白抑制剂（表皮细胞分化抑制剂）敏感的途径增强伪足形成并结合肌动蛋白重排，从而促进贴壁 Th1 型细胞的血渗。因此，Th1型选择性迁移的增强似乎是由Th1型细胞上的CCR5与内皮细胞产生的RANTES之间的相互作用诱导的血细胞渗出的原因。 CCR5 和 RANTES 在 Th1 型选择性迁移中发挥调节作用的进一步证据源自抗 RANTES 和抗 CCR5 Abs 消除了这种迁移。
Differentiated CD4 T cells can be divided into Th1 and Th2 types based on the cytokines they produce. Differential expression of chemokine receptors on either the Th1-type or the Th2-type cell suggests that Th1-type and Th2-type cells differ not only in cytokine production but also in their migratory capacity. Stimulation of endothelial cells with IFN-gamma selectively enhanced transmigration of Th1-type cells, but not Th2-type cells, in a transendothelial migration assay. Enhanced transmigration of Th1-type cells was dependent on the chemokine RANTES produced by endothelial cells, as indicated by the findings that Ab neutralizing RANTES, or Ab to its receptor CCR5, inhibited transmigration. Neutralizing Ab to chemokines macrophage-inflammatory protein-1alpha or monocyte chemotactic protein-1 did not inhibit Th1 selective migration. Whereas anti-CD18 and anti-CD54 blocked basal levels of Th1-type cell adherence to endothelial cells and also inhibited transmigration, anti-RANTES blocked only transmigration, indicating that RANTES appeared to induce transmigration of adherent T cells. RANTES seemed to promote diapedesis of adherent Th1-type cells by augmenting pseudopod formation in conjunction with actin rearrangement by a pathway that was sensitive to the phosphoinositol 3-kinase inhibitor wortmannin and to the Rho GTP-binding protein inhibitor, epidermal cell differentiation inhibitor. Thus, enhancement of Th1-type selective migration appeared to be responsible for the diapedesis induced by interaction between CCR5 on Th1-type cells and RANTES produced by endothelial cells. Further evidence that CCR5 and RANTES play a modulatory role in Th1-type selective migration derives from the abrogation of this migration by anti-RANTES and anti-CCR5 Abs.