NKG2D-RAE-1受体-配体变异不能解释非肥胖糖尿病小鼠的自然杀伤细胞缺陷。
NKG2D-RAE-1 receptor-ligand variation does not account for the NK cell defect in nonobese diabetic mice.
作者信息
Maier Lisa M, Howlett Sarah K, Rainbow Kara M, Clark Jan, Howson Joanna M M, Todd John A, Wicker Linda S
机构信息
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
出版信息
J Immunol. 2008 Nov 15;181(10):7073-80. doi: 10.4049/jimmunol.181.10.7073.
NK cells from NOD mice induced with poly(I:C) in vivo exhibit low cytotoxicity against a range of target cells, but the genetic mechanisms controlling this defect are yet to be elucidated. Defects in the expression of NKG2D and its ligands, the RAE-1 molecules, have been hypothesized to contribute to the reduced NK function present in NOD mice. In this study, we show that segregation of the NK-mediated killing phenotype did not correlate with the NOD Raet1 haplotype and that the large alterations in NKG2D expression previously reported on NK cells expanded in vitro were not observed in primary, poly(I:C)-elicited NK cells in vivo. Additional studies indicate a complex genetic control of defective NOD NK cells including genes linked to the MHC and possibly those that are associated with an altered cytokine response to the TLR3-agonist poly(I:C).
体内用聚肌胞苷酸（poly(I:C)）诱导的非肥胖糖尿病（NOD）小鼠的自然杀伤（NK）细胞对一系列靶细胞表现出低细胞毒性，但控制这种缺陷的遗传机制尚未阐明。有人推测，自然杀伤细胞活化受体2D（NKG2D）及其配体RAE-1分子表达的缺陷导致了NOD小鼠自然杀伤功能的降低。在本研究中，我们发现自然杀伤细胞介导的杀伤表型的分离与NOD小鼠的Raet1单倍型无关，并且在体内由聚肌胞苷酸诱导的原代自然杀伤细胞中未观察到先前报道的体外扩增的自然杀伤细胞上NKG2D表达的巨大变化。进一步的研究表明，NOD自然杀伤细胞缺陷存在复杂的遗传控制，包括与主要组织相容性复合体（MHC）相关的基因，以及可能与对Toll样受体3（TLR3）激动剂聚肌胞苷酸的细胞因子反应改变相关的基因。
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