期刊
CELL DEATH AND DIFFERENTIATION
卷 18, 期 7, 页码 1112-1119出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2011.5
关键词
T-killer cell; virus control; orphan granzymes; inflammation
资金
- Excellence Initiative of the German Federal and State Governments
- Deutsche Forschungsgemeinschaft [BO-1933, GRK1104]
- Ministerio de Ciencia e Innovacion (Spain) [SAF2008-02139]
- Gobierno de Aragon [PI076/08]
- [5RO1AI04494-03]
Granzymes (gzms) are key components of T-killer (Tc) cells believed to mediate pro-apoptotic activities. Recent evidence suggests that gzms also possess non-cytotoxic activities that contribute to host defense. In this study, we show that Tc cells from lymphocytic choriomeningitis virus (LCMV)-infected wild-type (wt) and gzm A/B-deficient mice express similar levels of gzmK protein, with both mouse strains efficiently controlling infection. GzmK, in recombinant form or secreted by ex vivo-derived LCMV-immune gzmAxB(-/-) Tc cells, lacks pro-apoptotic activity. Instead, gzmK induces primary mouse macrophages to process and secrete interleukin-1 beta, independent of the ATP receptor P2X(7). Together with the finding that IL-1Ra (Anakinra) treatment inhibits virus elimination but not generation of cytotoxic Tc cells in wt mice, the data suggest that Tc cells control LCMV through non-cytotoxic processes that involve gzmK. Cell Death and Differentiation (2011) 18, 1112-1119; doi:10.1038/cdd.2011.5; published online 11 February 2011
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