Leukocyte functional antigen 1 lowers T cell activation thresholds and signaling through cytohesin-1 and Jun-activating binding protein 1

被引:177
作者
Perez, OD
Mitchell, D
Jager, GC
South, S
Murriel, C
McBride, J
Herzenberg, LA
Kinoshita, S
Nolan, GP [1 ]
机构
[1] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA
[2] Stanford Univ, Baxter Lab Genet Pharmacol, Sch Med, Stanford, CA 94305 USA
[3] Stanford Univ, Dept Mol Pharmacol, Sch Med, Stanford, CA 94305 USA
[4] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA
[5] Stanford Univ, Dept Immunol & Rheumatol, Sch Med, Stanford, CA 94305 USA
[6] Univ Texas, SW Med Ctr, Dept Dermatol, Ctr Immunol, Dallas, TX 75390 USA
关键词
D O I
10.1038/ni984
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 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.
引用
收藏
页码:1083 / 1092
页数:10
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