Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.
Science. 2013 Dec 6;342(6163):1247-50. doi: 10.1126/science.1244689.
The centrosome is essential for cytotoxic T lymphocyte (CTL) function, contacting the plasma membrane and directing cytotoxic granules for secretion at the immunological synapse. Centrosome docking at the plasma membrane also occurs during cilia formation. The primary cilium, formed in nonhematopoietic cells, is essential for vertebrate Hedgehog (Hh) signaling. Lymphocytes do not form primary cilia, but we found and describe here that Hh signaling played an important role in CTL killing. T cell receptor activation, which "prearms" CTLs with cytotoxic granules, also initiated Hh signaling. Hh pathway activation occurred intracellularly and triggered Rac1 synthesis. These events "prearmed" CTLs for action by promoting the actin remodeling required for centrosome polarization and granule release. Thus, Hh signaling plays a role in CTL function, and the immunological synapse may represent a modified cilium.
中心体对于细胞毒性 T 淋巴细胞 (CTL) 的功能至关重要，它与质膜接触，并在免疫突触处指导细胞毒性颗粒进行分泌。中心体在纤毛形成过程中也与质膜对接。初级纤毛在非造血细胞中形成，对脊椎动物 Hedgehog (Hh) 信号传导至关重要。淋巴细胞不形成初级纤毛，但我们在这里发现并描述了 Hh 信号传导在 CTL 杀伤中起着重要作用。T 细胞受体激活会使 CTL 预先装备细胞毒性颗粒，同时也会引发 Hh 信号传导。Hh 途径的激活发生在细胞内，并触发 Rac1 的合成。这些事件通过促进中心体极化和颗粒释放所需的肌动蛋白重塑，为 CTL 的行动“预先武装”。因此，Hh 信号传导在 CTL 功能中发挥作用，免疫突触可能代表一种改良的纤毛。
