Capece Tara, Walling Brandon L, Lim Kihong, Kim Kyun-Do, Bae Seyeon, Chung Hung-Li, Topham David J, Kim Minsoo
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY.
Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY
J Cell Biol. 2017 Nov 6;216(11):3817-3829. doi: 10.1083/jcb.201609072. Epub 2017 Sep 27.
The integrin lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) is a key T cell adhesion receptor that mediates stable interactions with antigen-presenting cell (APC), as well as chemokine-mediated migration. Using our newly generated CD11a-mYFP knock-in mice, we discovered that naive CD8 T cells reserve a significant intracellular pool of LFA-1 in the uropod during migration. Intracellular LFA-1 quickly translocated to the cell surface with antigenic stimulus. Importantly, the redistribution of intracellular LFA-1 at the contact with APC was maintained during cell division and led to an unequal inheritance of LFA-1 in divided T cells. The daughter CD8 T cells with disparate LFA-1 expression showed different patterns of migration on ICAM-1, APC interactions, and tissue retention, as well as altered effector functions. In addition, we identified Rab27 as an important regulator of the intracellular LFA-1 translocation. Collectively, our data demonstrate that an intracellular pool of LFA-1 in naive CD8 T cells plays a key role in T cell activation and differentiation.
整合素淋巴细胞功能相关抗原1（LFA-1；CD11a/CD18）是一种关键的T细胞黏附受体，可介导与抗原呈递细胞（APC）的稳定相互作用以及趋化因子介导的迁移。利用我们新构建的CD11a-mYFP基因敲入小鼠，我们发现初始CD8⁺ T细胞在迁移过程中于尾足中储备了大量细胞内LFA-1库。细胞内LFA-1在抗原刺激下迅速转运至细胞表面。重要的是，细胞内LFA-1在与APC接触时的重新分布在细胞分裂过程中得以维持，并导致LFA-1在分裂的T细胞中出现不均等遗传。LFA-1表达不同的子代CD8⁺ T细胞在细胞间黏附分子1（ICAM-1）上呈现出不同的迁移模式、与APC的相互作用及组织滞留情况，其效应功能也发生了改变。此外，我们确定Rab27是细胞内LFA-1转运的重要调节因子。总体而言，我们的数据表明，初始CD8⁺ T细胞中的细胞内LFA-1库在T细胞活化和分化中起关键作用。
