Salazar-Fontana Laura Inés, Barr Valarie, Samelson Lawrence E, Bierer Barbara E
Laboratory of Lymphocyte Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2003 Sep 1;171(5):2225-32. doi: 10.4049/jimmunol.171.5.2225.
Engagement of the costimulatory molecule CD28 is an important step in the optimal activation of T cells. Nevertheless, the specific role of CD28 in the formation of the immunological synapse and cytoskeletal changes that occur upon TCR/CD3 complex engagement is still poorly understood. Using Ab-coated surfaces, we show that CD28 engagement in the absence of any other signal induced the formation of cytoplasmic elongations enriched in filamentous actin (F-actin), in this work called filopodia or microspikes. Such structures were specific for engagement of CD28 on mAb-coated surfaces because they could not be observed in surfaces coated with either poly(L-lysine) or anti-CD3 mAb. The signaling pathway coupling CD28 to cytoskeletal rearrangements required Src-related kinase activity and promoted Vav phosphorylation and Cdc42 activation independently of the zeta-chain-associated kinase (ZAP-70). CD28-induced filopodia required Cdc42 GTPase activity, but not the related Rho GTPase Rac1. Moreover, Cdc42 colocalized to areas of increased F-actin. Our results support a specific role for the activation of the small Rho GTPase Cdc42 in the actin reorganization mediated by CD28 in human T cells.
共刺激分子CD28的参与是T细胞最佳激活过程中的重要一步。然而，CD28在免疫突触形成以及TCR/CD3复合物参与后发生的细胞骨架变化中的具体作用仍知之甚少。利用抗体包被的表面，我们发现，在没有任何其他信号的情况下，CD28的参与会诱导富含丝状肌动蛋白（F-肌动蛋白）的细胞质延伸结构的形成，在本研究中称为丝状伪足或微刺。这些结构是CD28在单克隆抗体包被表面上参与的特异性表现，因为在聚（L-赖氨酸）或抗CD3单克隆抗体包被的表面上无法观察到它们。将CD28与细胞骨架重排偶联的信号通路需要Src相关激酶活性，并独立于ζ链相关激酶（ZAP-70）促进Vav磷酸化和Cdc42激活。CD28诱导的丝状伪足需要Cdc42 GTP酶活性，但不需要相关的Rho GTP酶Rac1。此外，Cdc42与F-肌动蛋白增加的区域共定位。我们的结果支持小Rho GTP酶Cdc42的激活在人T细胞中由CD28介导的肌动蛋白重组中具有特定作用。
