Perez Omar D, Mitchell Dennis, Jager Gina C, South Sharon, Murriel Chris, McBride Jacqueline, Herzenberg Lee A, Kinoshita Shigemi, Nolan Garry P
Department of Microbiology and Immunology, and The Baxter Laboratory of Genetic Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA.
Nat Immunol. 2003 Nov;4(11):1083-92. doi: 10.1038/ni984. Epub 2003 Oct 5.
Leukocyte functional antigen 1 (LFA-1), with intercellular adhesion molecule ligands, mediates T cell adhesion, but the signaling pathways and functional effects imparted by LFA-1 are unclear. Here, intracellular phosphoprotein staining with 13-dimensional flow cytometry showed that LFA-1 activation induced phosphorylation of the beta(2) integrin chain and release of Jun-activating binding protein 1 (JAB-1), and mediated signaling of kinase Erk1/2 through cytohesin-1. Dominant negatives of both JAB-1 and cytohesin-1 inhibited interleukin 2 production and impaired T helper type 1 differentiation. LFA-1 stimulation lowered the threshold of T cell activation. Thus, LFA-1 signaling contributes to T cell activation and effects T cell differentiation.
白细胞功能抗原1（LFA-1）与细胞间黏附分子配体一起介导T细胞黏附，但LFA-1所赋予的信号通路和功能效应尚不清楚。在这里，通过13维流式细胞术进行的细胞内磷蛋白染色显示，LFA-1激活诱导β2整合素链磷酸化以及Jun激活结合蛋白1（JAB-1）的释放，并通过细胞衔接蛋白1介导激酶Erk1/2的信号传导。JAB-1和细胞衔接蛋白1的显性负性突变体抑制白细胞介素2的产生并损害1型辅助性T细胞分化。LFA-1刺激降低了T细胞激活的阈值。因此，LFA-1信号传导有助于T细胞激活并影响T细胞分化。
