Involvement of NKR-P2/NKG2D in DC-mediated killing of tumor targets: indicative of a common, innate, target-recognition paradigm?

被引:19
作者
Alli, R [1 ]
Savithri, B [1 ]
Das, S [1 ]
Varalakshmi, C [1 ]
Rangaraj, N [1 ]
Khar, A [1 ]
机构
[1] Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India
关键词
dendritic cell; NKR-P2; reorganization; apoptosis; TNF-alpha;
D O I
10.1002/eji.200324793
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
DC are the most efficient antigen-presenting cells that regulate the immune response. Here, we demonstrate the expression of NK cell receptor protein-2 (NKR-P2) on rat and mouse DC, and we show that NKR-P2 gets reorganized upon antigen contact. DC activated with anti-NKR-P2 mAb exhibit enhanced apoptotic killing of tumor targets, whereas blocking the interaction between NKR-P2 and its ligand with rNKR-P2 abrogated apoptotic killing, suggesting NKR-P2 to function as an activating molecule on DC. In vivo injection of anti-NKR-P2 mAb augmented DC activity and delayed tumor progression. NKR-P2 signaling involved Ca2+ influx, culminating in the expression of the apoptosis-inducing molecule, TNF-alpha. Taken together, these observations suggest that NKR-P2 (the rat orthologue of human NKG2D) acts as a target-recognition molecule on DC.
引用
收藏
页码:1119 / 1126
页数:8
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