Departamento de Bioquímica, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico.
Tohoku J Exp Med. 2010 Aug;221(4):271-9. doi: 10.1620/tjem.221.271.
Activation of CD4(+) T cells plays a main role in adaptive immune response by regulating cellular and humoral immunity via processes associated with changes in cell surface oligosaccharide receptors. Lectins are glycoproteins that specifically recognize oligosaccharides and have been used to characterize changes in oligosaccharides present on T cell surface and their effects on activation. A lectin from Amaranthus leucocarpus seeds (ALL) is specific for glycoprotein structures containing galactose-N-acetylgalactosamine and is able to bind to human and murine CD4(+) T cells, however, its effect on activation remains unclear. We examined the effect of ALL on the activation of peripheral blood human CD4(+) T cells and analyzed cell proliferation, expression of the activation-associated molecule CD25, secretion of the activation-dependent cytokine interleukin (IL)-2 and intracellular calcium influx changes using flow cytometry. CD4(+) T cells were stimulated with anti-CD3 antibodies that provided the first activation signal in the presence or absence of ALL. ALL alone did not induce CD4(+) T cell activation but when also stimulated with anti-CD3 antibodies, ALL up-regulated CD25 expression, cell proliferation, IL-2 secretion and an intracellular calcium influx in a dose-dependent manner. In addition, ALL recognized CD4(+) T cells expressing the CD69 and Ki67 molecules expressed only by activated T cells and induced production of the TH1-type cytokine interferon-gamma. Our findings indicate that ALL binds to human activated CD4(+) T cells and enhances the degree of activation of CD4(+) T cells that are stimulated with anti-CD3 antibodies. ALL provides a new tool for analyzing T cell activation mechanisms.
CD4(+) T 细胞的激活通过与细胞表面寡糖受体变化相关的过程调节细胞和体液免疫,从而在适应性免疫反应中发挥主要作用。凝集素是特异性识别寡糖的糖蛋白,已被用于表征 T 细胞表面存在的寡糖变化及其对激活的影响。来自苋菜(Amaranthus leucocarpus)种子的凝集素(ALL)特异性识别含有半乳糖-N-乙酰半乳糖胺的糖蛋白结构,能够与人和鼠的 CD4(+) T 细胞结合,但其对激活的影响尚不清楚。我们研究了 ALL 对人外周血 CD4(+) T 细胞激活的影响,并使用流式细胞术分析了细胞增殖、激活相关分子 CD25 的表达、激活依赖性细胞因子白细胞介素(IL)-2 的分泌以及细胞内钙离子流入的变化。CD4(+) T 细胞在存在或不存在 ALL 的情况下,用抗 CD3 抗体刺激以提供第一激活信号。ALL 本身不能诱导 CD4(+) T 细胞激活,但与抗 CD3 抗体一起刺激时,ALL 以剂量依赖的方式上调 CD25 表达、细胞增殖、IL-2 分泌和细胞内钙离子流入。此外,ALL 识别仅在激活的 T 细胞中表达的 CD4(+) T 细胞上表达的 CD69 和 Ki67 分子,并诱导 TH1 型细胞因子干扰素-γ的产生。我们的研究结果表明,ALL 与人类激活的 CD4(+) T 细胞结合,并增强了用抗 CD3 抗体刺激的 CD4(+) T 细胞的激活程度。ALL 为分析 T 细胞激活机制提供了一种新的工具。