Blaser C, Kaufmann M, Müller C, Zimmermann C, Wells V, Mallucci L, Pircher H
Institute for Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Germany.
Eur J Immunol. 1998 Aug;28(8):2311-9. doi: 10.1002/(SICI)1521-4141(199808)28:08<2311::AID-IMMU2311>3.0.CO;2-G.
We have used mRNA differential display PCR to search for genes induced in activated T cells and have found the LGALS1 (lectin, galactoside-binding, soluble) gene to be strongly up-regulated in effector T cells. The protein coded by the LGALS1 gene is a beta-galactoside-binding protein (betaGBP), which is released by cells as a monomeric negative growth factor but which can also associate into homodimers (galectin-1) with lectin properties. Northern blot analysis revealed that ex vivo isolated CD8+ effector T cells induced by a viral infection expressed high amounts of LGALS1 mRNA, whereas LGALS1 expression was almost absent in resting CD8+ T cells. LGALS1 expression could be induced in CD4+ and CD8+ T cells upon activation with the cognate peptide antigen and high levels of LGALS1 expression were found in concanavalin A-activated T cells but not in lipopolysaccharide-activated B cells. Gel filtration and Western blot analysis revealed that only monomeric betaGBP was released by activated CD8+ T cells and in vitro experiments further showed that recombinant betaGBP was able to inhibit antigen-induced proliferation of naive and antigen-experienced CD8+ T cells. Thus, these data indicate a role of betaGBP as an autocrine negative growth factor for CD8+ T cells.
我们利用mRNA差异显示PCR技术寻找活化T细胞中诱导表达的基因,发现LGALS1(凝集素,半乳糖苷结合,可溶性)基因在效应T细胞中强烈上调。LGALS1基因编码的蛋白质是一种β-半乳糖苷结合蛋白(βGBP),它作为一种单体负生长因子从细胞中释放出来,但也可以结合形成具有凝集素特性的同型二聚体(半乳糖凝集素-1)。Northern印迹分析显示,病毒感染诱导的体外分离的CD8+效应T细胞表达大量LGALS1 mRNA,而静息CD8+ T细胞中几乎不存在LGALS1表达。用同源肽抗原激活后,CD4+和CD8+ T细胞中可诱导LGALS1表达,在伴刀豆球蛋白A激活的T细胞中发现高水平的LGALS1表达,而在脂多糖激活的B细胞中未发现。凝胶过滤和Western印迹分析显示,活化的CD8+ T细胞仅释放单体βGBP,体外实验进一步表明重组βGBP能够抑制抗原诱导的幼稚和抗原致敏CD8+ T细胞的增殖。因此,这些数据表明βGBP作为CD8+ T细胞的自分泌负生长因子发挥作用。