Hogg Nancy, Laschinger Melanie, Giles Katherine, McDowall Alison
Leukocyte Adhesion Laboratory, Cancer Research UK London Research Institute, London WC2A 3PX, UK.
J Cell Sci. 2003 Dec 1;116(Pt 23):4695-705. doi: 10.1242/jcs.00876.
T cells use integrins in essentially all of their functions. They use integrins to migrate in and out of lymph nodes and, following infection, to migrate into other tissues. At the beginning of an immune response, integrins also participate in the immunological synapse formed between T cells and antigen-presenting cells. Because the ligands for integrins are widely expressed, integrin activity on T cells must be tightly controlled. Integrins become active following signalling through other membrane receptors, which cause both affinity alteration and an increase in integrin clustering. Lipid raft localization may increase integrin activity. Signalling pathways involving ADAP, Vav-1 and SKAP-55, as well as Rap1 and RAPL, cause clustering of leukocyte function-associated antigen-1 (LFA-1; integrin alphaLbeta2). T-cell integrins can also signal, and the pathways dedicated to the migratory activity of T cells have been the most investigated so far. Active LFA-1 causes T-cell attachment and lamellipodial movement induced by myosin light chain kinase at the leading edge, whereas RhoA and ROCK cause T-cell detachment at the trailing edge. Another important signalling pathway acts through CasL/Crk, which might regulate the activity of the GTPases Rac and Rap1 that have important roles in T-cell migration.
T细胞在其几乎所有功能中都会用到整合素。它们利用整合素在淋巴结内外迁移，并且在感染后迁移至其他组织。在免疫反应开始时，整合素也参与T细胞与抗原呈递细胞之间形成的免疫突触。由于整合素的配体广泛表达，因此T细胞上整合素的活性必须受到严格控制。通过其他膜受体发出信号后，整合素会变得活跃，这会导致亲和力改变以及整合素聚集增加。脂筏定位可能会增加整合素活性。涉及ADAP、Vav-1和SKAP-55以及Rap1和RAPL的信号通路会导致白细胞功能相关抗原-1（LFA-1；整合素αLβ2）聚集。T细胞整合素也可以发出信号，并且迄今为止，对专门负责T细胞迁移活性的信号通路研究得最多。活跃的LFA-1会导致T细胞附着以及肌球蛋白轻链激酶在前缘诱导的片状伪足运动，而RhoA和ROCK会导致T细胞在后缘脱离。另一条重要的信号通路通过CasL/Crk起作用，它可能会调节在T细胞迁移中起重要作用的GTP酶Rac和Rap1的活性。
