van den Broek M F, Müller U, Huang S, Aguet M, Zinkernagel R M
Institute of Experimental Immunology, University of Zürich, Switzerland.
J Virol. 1995 Aug;69(8):4792-6. doi: 10.1128/JVI.69.8.4792-4796.1995.
Alpha/beta interferon (IFN) and gamma IFN exert widely overlapping biological effects. Still, mice with individually inactivated alpha/beta or gamma receptors exhibit variably severely reduced resistance to infection and altered immune responses. To investigate to what extent the two IFN systems are functionally redundant, we generated mice with a combined receptor defect (AG129 mice). Like mice with individual mutations, AG129 mice had no apparent anomalies, confirming that in the mouse the IFN system is not essential for normal development. These mice showed an additive phenotype with respect to antiviral defense and exhibited an increased susceptibility to lymphocytic choriomeningitis virus (LCMV) and notably vaccinia virus infection. Because of unlimited replication and subsequent rapid exhaustion of cytotoxic T lymphocyte (CTL) precursors, these mice were unable to mount a CTL response to LCMV. CD8(+)-mediated immunopathology was absent in LCMV-infected mice, and virus persisted. Vaccinia virus replicated much faster in AG129 mice, and a 10(4)-fold lower dose of vaccinia virus was sufficient to prime these mice. With the normal priming dose of 10(6) PFU, cytopathic effects and overwhelming infection possibly causing partial exhaustion of CTL interfered with the anti-vaccinia virus response. Even though global antiviral immunoglobulin G (IgG) titers were within normal ranges, the IgG subclass distribution was heavily biased toward IgG1.
α/β干扰素（IFN）和γ干扰素具有广泛重叠的生物学效应。然而，α/β或γ受体单独失活的小鼠对感染的抵抗力呈现出不同程度的严重降低，免疫反应也发生改变。为了研究这两种干扰素系统在功能上的冗余程度，我们培育了具有联合受体缺陷的小鼠（AG129小鼠）。与具有单个突变的小鼠一样，AG129小鼠没有明显异常，这证实了在小鼠中干扰素系统对于正常发育并非必不可少。这些小鼠在抗病毒防御方面表现出累加表型，并且对淋巴细胞性脉络丛脑膜炎病毒（LCMV），尤其是痘苗病毒感染的易感性增加。由于细胞毒性T淋巴细胞（CTL）前体的无限制复制及随后的快速耗竭，这些小鼠无法对LCMV产生CTL反应。在感染LCMV的小鼠中不存在CD8(+)介导的免疫病理反应，病毒持续存在。痘苗病毒在AG129小鼠中的复制速度要快得多，低10(4)倍剂量的痘苗病毒就足以使这些小鼠致敏。使用10(6) PFU的正常致敏剂量时，细胞病变效应和可能导致CTL部分耗竭的压倒性感染干扰了抗痘苗病毒反应。尽管总体抗病毒免疫球蛋白G（IgG）滴度在正常范围内，但IgG亚类分布严重偏向IgG1。
