Rodriguez Marisela, Sabastian Pearl, Clark Patricia, Brown Michael G
Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
J Immunol. 2004 Nov 15;173(10):6312-8. doi: 10.4049/jimmunol.173.10.6312.
Ly49H(+) NK cells play a critical role in innate antiviral immune responses to murine CMV (MCMV). Ly49H(b6) recognition of MCMV-encoded m157 on infected cells activates natural killing required for host resistance. We show that mAb 3D10 (anti-Ly49H) recognizes comparable subsets of NK cells from New Zealand White (NZW), New Zealand Black (NZB), and C57BL/6 spleens. However, virus levels in the spleens of MCMV-infected NZW and NZB mice differed greatly. We found that MCMV replication in infected NZW spleens was limited through NK cells. Alternately, NZB mice were profoundly susceptible to MCMV infection. Although 3D10 mAb injections given before infection interfere with Cmv1-type resistance in C57BL/6 mice, similar mAb injections did not affect NZW resistance, likely because NZW NK cell receptors did not bind MCMV-encoded m157. Instead, anti-MCMV host defenses in hybrid NZ offspring were associated with multiple chromosome locations including several putative quantitative trait loci that did not overlap with H-2 or NK gene complex loci. This study revealed a novel pathway used by NK cells to defend against MCMV infection. Thus, the importance of Ly49H in MCMV infection may be shaped by other additional background genes.
Ly49H(+)自然杀伤细胞（NK细胞）在对鼠巨细胞病毒（MCMV）的先天性抗病毒免疫反应中起关键作用。Ly49H(b6)对感染细胞上MCMV编码的m157的识别激活了宿主抵抗所需的自然杀伤作用。我们发现单克隆抗体3D10（抗Ly49H）识别来自新西兰白兔（NZW）、新西兰黑兔（NZB）和C57BL/6脾脏的相当数量的NK细胞亚群。然而，MCMV感染的NZW和NZB小鼠脾脏中的病毒水平差异很大。我们发现，感染的NZW脾脏中MCMV的复制通过NK细胞受到限制。相反，NZB小鼠对MCMV感染极为敏感。虽然在感染前注射3D10单克隆抗体可干扰C57BL/6小鼠的Cmv1型抗性，但类似的单克隆抗体注射并不影响NZW的抗性，可能是因为NZW NK细胞受体不与MCMV编码的m157结合。相反，杂交NZB后代中的抗MCMV宿主防御与多个染色体位置相关，包括几个推定的数量性状位点，这些位点与H-2或NK基因复合体位点不重叠。这项研究揭示了NK细胞用于抵御MCMV感染的一条新途径。因此，Ly49H在MCMV感染中的重要性可能受其他额外背景基因的影响。
