Measles virus contact with T cells impedes cytoskeletal remodeling associated with spreading, polarization, and CD3 clustering
Measles virus contact with T cells impedes cytoskeletal remodeling associated with spreading, polarization, and CD3 clustering
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DOI：
10.1111/j.1600-0854.2006.00426.x
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发表时间：
2006-07-01
期刊：
影响因子：
4.5
通讯作者：
Schneider-Schaulies, Sibylle
中科院分区：
文献类型：
--
作者：
Muller, Nora;Avota, Elita;Schneider-Schaulies, Sibylle
接触麻疹病毒（MV）糖蛋白（gp）复合物后，CD3/ cd28诱导的PI3/Akt激酶通路激活和T细胞增殖受损。我们现在表明，这个信号也会损害T细胞中的肌动蛋白细胞骨架重塑，从而使其失去粘附和促进微绒毛形成的能力。MV暴露导致膜突几乎完全塌陷，与cofilin和ezrin/radixin/moesin （ERM）蛋白磷酸化水平降低有关。暴露于MV的T细胞无法激活Cdc42和Rac1以响应CD3/CD28的连接，这与它们无法获得与扩散和板足形成一致的形态一致。尽管这些细胞骨架驱动的形态学改变的损伤，这些细胞被招募到与树突状细胞结合，有效地作为对照T细胞。然而，MV引发的信号阻止了T细胞的极化，这是由微管组织中心向突触重新分配的失败所证明的。此外，CD3不能有效地聚集和重新分配到免疫突触的中心区域。因此，通过诱导微绒毛塌陷和干扰细胞骨架重塑，MV信号干扰了T细胞粘附、扩散和聚集受体的能力，这些受体是T细胞持续活化所必需的。
CD3/CD28-induced activation of the PI3/Akt kinase pathway and proliferation is impaired in T cells after contact with the measles virus (MV) glycoprotein (gp) complex. We now show that this signal also impairs actin cytoskeletal remodeling in T cells, which loose their ability to adhere and to promote microvilli formation. MV exposure results in an almost complete collapse of membrane protrusions associated with reduced phosphorylation levels of cofilin and ezrin/radixin/moesin (ERM) proteins. Consistent with their inability to activate Cdc42 and Rac1 in response to the ligation of CD3/CD28, T cells exposed to MV fail to acquire a morphology consistent with spreading and lamellopodia formation. In spite of these impairments of cytoskeleton-driven morphological alterations, these cells are recruited into conjugates with dendritic cells as efficiently as control T cells. The signal elicited by MV, however, prevents T cells to polarize as documented by a failure to redistribute the microtubule organizing center toward the synapse. Moreover, CD3 cannot be efficiently clustered and redistributed to the central region of the immunological synapse. Thus, by inducing microvillar collapse and interfering with cytoskeletal remodeling, MV signaling disturbs the ability of T cells to adhere, spread, and cluster receptors essential for sustained T-cell activation.