The effect of the Cmv-1 resistance gene, which is linked to the natural killer cell gene complex, is mediated by natural killer cells.
The effect of the Cmv-1 resistance gene, which is linked to the natural killer cell gene complex, is mediated by natural killer cells.
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Cmv-1 抗性基因与自然杀伤细胞基因复合体相连，其作用是由自然杀伤细胞介导的。
作者：
A. Scalzo;N. A. Fitzgerald;C. R. Wallace;A. E. Gibbons;Y. Smart;R. Burton;G. Shellam
小鼠对鼠巨细胞病毒（MCMV）致死性感染的抵抗力受到复杂的宿主遗传控制，H-2和非H-2基因都有贡献。我们以前已经表明，一个常染色体，非MHC编码的基因，CMV-1，控制MCMV在脾脏中的复制。我们研究了CMV-1抗性基因对MCMV感染的保护机制。使用H-2兼容的辐射骨髓嵌合体，增强的抵抗MCMV感染，这是与C57 BL背景中的Cmv-11等位基因被证明是由辐射敏感的骨髓衍生的细胞群，或这些细胞产生的因子介导的。在CXB重组近交系小鼠品系中，血清IFN滴度与CMV-1的品系分布模式之间缺乏相关性，这表明IFN不介导该基因赋予的抗性。类似地，在C57 BL/6J小鼠中缺乏体内耗尽成熟的CD4+和CD8 + T细胞对病毒复制的影响表明T细胞不太可能参与。相反，通过注射抗NK 1.1 mAb PK 136体内耗竭NK细胞，可消除C57 BL/6 J-BALB. B嵌合小鼠和CMV-11 CX B株中的限制性脾病毒复制。这些数据表明，CMV-1基因的作用是由NK细胞介导的。易感Cmv-1h株（BALB/cBy、CXBG/By、CXBH/By、CXBI/By和CXBK/By）MCMV感染后NK细胞活性显著增强，表明这些小鼠中存在功能和表型不同于Cmv-1l株的NK细胞。Cmv-1h株中存在的NK细胞不能有效地限制脾MCMV在体内的复制，这可能是由于对病毒感染的靶细胞缺乏特异性。最后，流式细胞术分析NK1 - 1在CXB和BXD RI小鼠中的表达以及MCMV在BXD RI株中的复制研究表明，Cmv-1与NK1.1和位于小鼠6号染色体远端片段上的其他位点紧密连锁，该区域最近被定义为自然杀伤复合体。
The resistance of mice to lethal infection by murine CMV (MCMV) is under complex host genetic control with contributions from both H-2 and non-H-2 genes. We have previously shown that an autosomal, non-MHC encoded gene, Cmv-1, controls MCMV replication in the spleen. We have investigated the mechanism by which the Cmv-1 resistance gene confers protection against MCMV infection. Using H-2 compatible irradiation bone marrow chimeras, the enhanced resistance to MCMV infection that is associated with the Cmv-1l allele in the C57BL background was shown to be mediated by an irradiation-sensitive bone marrow-derived cell population, or a factor produced by these cells. The lack of correlation between serum IFN titers and the strain distribution pattern of Cmv-1 in CXB recombinant inbred mouse strains suggests that IFN does not mediate resistance conferred by this gene. Similarly, the lack of effect of in vivo depletion of mature CD4+ and CD8+ T cells on virus replication in C57BL/6J mice indicates that T cells are unlikely to be involved. In contrast, in vivo depletion of NK cells by injection of the anti-NK1.1 mAb PK136 abrogated restricted splenic virus replication in C57BL/6J----BALB.B chimeric mice and in the Cmv-1l CXB strains. These data indicate that the effect of the Cmv-1 gene is mediated by NK cells. The significant augmentation in NK cell activity after MCMV infection of the susceptible Cmv-1h strains (BALB/cBy), CXBG/By, CXBH/By, CXBI/By, and CXBK/By) indicates the existence in these mice of NK cells that are functionally and phenotypically distinct from those in Cmv-1l strains. NK cells present in the Cmv-1h strains are unable to restrict efficiently splenic MCMV replication in vivo, possibly due to a lack of specificity for virus-infected target cells. Finally, flow cytometric analysis of NK1-1 expression in CXB and BXD RI mice together with MCMV replication studies in the BXD RI strains indicate that Cmv-1 is closely linked to NK1.1 and other loci that reside on a distal segment of murine chromosome 6 in a region that has recently been defined as the natural killer complex.