Enhancement of CD8 T-cell function through modifying surface glycoproteins in young and old mice

被引:21
作者
Akha, Amir A. Sadighi
Berger, Scott B.
Miller, Richard A.
机构
[1] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA
[2] Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Sch Med, Geriatr Ctr, Ann Arbor, MI 48109 USA
[4] Ann Arbor DVA Med Ctr, Ann Arbor, MI USA
关键词
rodent; ageing; TCR; signal transduction; glycosylation;
D O I
10.1111/j.1365-2567.2006.02420.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Previous work from our laboratory has shown that modifying cell surface glycosylation with either a Clostridium perfringens-derived sialidase (CP-Siase), or an O-linked glycoprotein endopeptidase (OSGE) can enhance the function of CD4 T cells from both young and old mice at multiple levels. Here we have re-assessed the effect of age on CD8 T-cell function, and examined the outcome of enzymatic treatment with CP-Siase and OSGE on its different aspects. Pre-treatment of CD8 T cells with either CP-Siase or OSGE led to a significant increase in anti-CD3-mediated Ca2+ response in both young and old mice. Pre-treated CD8 T cells from both age groups also displayed a significant increase in activation-induced CD69 and CD25 expression, and produced significantly higher amounts of interleukin-2 and interferon-gamma in comparison to their untreated counterparts. Furthermore, pretreatment with either enzyme enhanced granzyme B expression in CD8 T cells, and increased their cytolytic activity in vitro. These data support the notion that glycosylated surface proteins hinder CD8 T-cell activation and function in both young and old mice, and raise the possibility of significantly improving CD8 T cell function in older individuals through enzymatic alteration of surface glycoproteins.
引用
收藏
页码:187 / 194
页数:8
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