Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs

被引：352

作者：

Fehniger, Todd A.

Cai, Sheng F.

Cao, Xuefan

Bredemeyer, Andrew J.

Presti, Rachel Im.

French, Anthony R. ^{[1
]}

Ley, Timothy J.

机构：

[1] Washington Univ, Sch Med, Siteman Canc Ctr, Dept Pediat,Div Rheumatol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Siteman Canc Ctr, Dept Internal Med,Div Oncol, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Siteman Canc Ctr, Dept Internal Med,Div Infect Dis, St Louis, MO 63110 USA

来源：

IMMUNITY | 2007年 / 26卷 / 06期

关键词：

D O I：

10.1016/j.immuni.2007.04.010

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Although activated murine NK cells can use the granule exocytosis pathway to kill target cells immediately upon recognition, resting murine NK cells are minimally cytotoxic for unknown reasons. Here, we showed that resting NK cells contained abundant granzyme A, but little granzyme B or perforin; in contrast, the mRNAs for all three genes were abundant. Cytokine-induced in vitro activation of NK cells resulted in potent cytotoxicity associated with a dramatic increase in granzyme B and perforin, but only minimal changes in mRNA abundance for these genes. The same pattern of regulation was found in vivo with murine cytomegalovirus infection as a physiologic model of NK cell activation. These data suggest that resting murine NK cells are minimally cytotoxic because of a block in perforin and granzyme B mRNA translation that is released by NK cell activation.

引用

页码：798 / 811

页数：14

共 61 条

[1] Perforin is not co-expressed with granzyme A within cytotoxic granules in CD8 T lymphocytes present in lymphoid tissue during chronic HIV infection [J].