Sustained NKG2D engagement induces cross-tolerance of multiple distinct NK cell activation pathways

被引:141
作者
Coudert, Jerome D. [1 ,2 ]
Scarpellino, Loenardo [1 ,2 ]
Gros, Frederic [1 ,2 ]
Vivier, Eric [3 ,4 ,5 ]
Held, Werner [1 ,2 ]
机构
[1] Ludwig Inst Canc Res, Lausanne Branch, CH-1066 Epalinges, Switzerland
[2] Univ Lausanne, CH-1015 Lausanne, Switzerland
[3] Univ Mediterranee, Ctr Immunol Marseille Luminy, Marseille, France
[4] INSERM, U631, F-13258 Marseille, France
[5] CNRS, UMR 6102, F-75700 Paris, France
关键词
D O I
10.1182/blood-2007-07-100057
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
NKG2D is a multisubunit activation receptor that allows natural killer (NK) cells to detect and eliminate stressed, infected, and transformed host cells. However, the chronic exposure of NK cells to cell-bound NKG2D ligands has been shown to impair NKG2D function both in vitro and in vivo. Here we have tested whether continuous NKG2D engagement selectively impacted NKG2D function or whether heterologous NK cell activation pathways were also affected. We found that sustained NKG2D engagement induced cross-tolerization of several unrelated NK cell activation receptors. We show that receptors that activate NK cells via the DAP12/KARAP and DAP1 0 signaling adaptors, such as murine NKG2D and Ly49D, cross-tolerize preferentially NK cell activation pathways that function independent of DAP10/12, such as antibody-dependent cell-mediated cytotoxicity and missing-self recognition. Conversely, DAP10/12-independent pathways are unable to cross-tolerize unrelated NK cell activation receptors such as NKG2D or Ly49D. These data define a class of NK cell activation receptors that can tolerize mature NK cells. The reversible suppression of the NK cells' cytolytic function probably reduces the NK cells' efficacy to control endogenous and exogenous stress yet may be needed to limit tissue damage.
引用
收藏
页码:3571 / 3578
页数:8
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