Berger Scott B, Sadighi Akha Amir A, Miller Richard A
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, USA.
Int Immunol. 2005 Aug;17(8):983-91. doi: 10.1093/intimm/dxh279. Epub 2005 Jul 6.
Many of the downstream signaling defects observed in aged T cells are believed to be the result of very early events involving the initial interaction between T cells and antigen-presenting cells. Recent findings suggest that this interaction is hindered by glycosylated surface macromolecules, including CD43, on the T cell surface. Treatment of CD4+ T cells by O-sialoglycoprotein endopeptidase (OSGE), which cleaves glycosylated forms of CD43, restores the ability of cells from aged mice to form immunological synapses and to express early activation markers. Here we show that OSGE enhances Ca2+ influx in T cells from CB6F1 mice, and enhances their ability to produce IL-2, IL-4, IL-5, IL-6, IL-10, IL-13 and IFNgamma at the mRNA level, and IL-2 and IFNgamma at the protein level, in the first 6 h after activation. Although OSGE has little effect on synapse formation in CD4+ T cells from young mice, our new data show that OSGE increases the production of most cytokines by young as well as old T cells. Secretion of the T(h)2 cytokine, IL-4, was altered only slightly by OSGE treatment, suggesting that the removal of OSGE-sensitive surface molecules may have differential effects on T(h)1 and T(h)2 cytokines. These data support a model in which O-glycosylated surface proteins inhibit CD4+ lymphocyte activation in both young and old mice, and in which such glycoproteins contribute to the age-related decline in cytokine production.
许多在衰老T细胞中观察到的下游信号缺陷被认为是涉及T细胞与抗原呈递细胞初始相互作用的早期事件的结果。最近的研究结果表明，这种相互作用受到T细胞表面糖基化表面大分子（包括CD43）的阻碍。用O-唾液酸糖蛋白内肽酶（OSGE）处理CD4+T细胞，该酶可切割CD43的糖基化形式，可恢复衰老小鼠细胞形成免疫突触和表达早期激活标志物的能力。在这里，我们表明OSGE增强了CB6F1小鼠T细胞中的Ca2+内流，并增强了它们在激活后最初6小时内在mRNA水平上产生IL-2、IL-4、IL-5、IL-6、IL-10、IL-13和IFNγ以及在蛋白质水平上产生IL-2和IFNγ的能力。虽然OSGE对年轻小鼠CD4+T细胞中的突触形成影响很小，但我们的新数据表明，OSGE增加了年轻和衰老T细胞中大多数细胞因子的产生。OSGE处理对T(h)2细胞因子IL-4的分泌影响很小，这表明去除对OSGE敏感的表面分子可能对T(h)1和T(h)2细胞因子有不同的影响。这些数据支持了一个模型，即O-糖基化表面蛋白在年轻和衰老小鼠中均抑制CD4+淋巴细胞激活，并且这些糖蛋白导致细胞因子产生与年龄相关的下降。
