Kohl S, Loo L S
J Immunol. 1982 Jul;129(1):370-6.
Infant mice are extremely susceptible to fatal Herpes simplex virus (HSV) infection. They are unable to produce antibody to HSV, and their leukocytes cannot mediate antibody-dependent cellular cytotoxicity (ADCC) to HSV-infected cells. In order to avoid H-2-dependent effector mechanisms and instead analyze possible in vivo ADCC, a murine model employing adoptive transfer of antibody and human leukocytes was developed. Administration of either human immune globulin or leukocytes i.p. from HSV immune or nonimmune humans could not protect infant C57BL/6 mice from fatal HSV infection. In contrast, a combination of a subneutralizing dilution of globulin and leukocytes from nonimmune or immune human donors, given one day before inoculation, was highly protective against lethal HSV infection. The cells involved included lymphocytes or monocyte-macrophages. At least 5 X 10(6) viable leukocytes (or 1 X 10(6) monocyte-macrophages) and immune serum globulin concentrations as low as 10(-8) were protective. Infected cell monolayer adsorption and DEAE column fractionation demonstrated that the protection by globulin was due to specific antiviral IgG antibody. Protection was n ot seen in animals receiving virus before immune transfer. Protection did not involve synergistic viral neutralization by antibody and cells, as shown by in vitro experiments. Animals receiving globulin and cells, unlike normal infant mice, had circulating antiviral antibody and peritoneal leukocytes able to mediate ADCC to HSV-infected cells. This is the first in vivo evidence for the role of human ADCC. This model also allows for the in vivo evaluation of the ability of cells from immunocompromised humans to curb viral infection.
幼鼠极易受到单纯疱疹病毒（HSV）致命感染。它们无法产生针对HSV的抗体，其白细胞也不能介导对HSV感染细胞的抗体依赖性细胞毒性（ADCC）。为了避免H - 2依赖性效应机制，转而分析可能的体内ADCC，开发了一种采用抗体和人白细胞过继转移的小鼠模型。给幼龄C57BL / 6小鼠腹腔注射来自HSV免疫或非免疫人类的人免疫球蛋白或白细胞，均不能保护它们免受致命的HSV感染。相比之下，在接种前一天给予来自非免疫或免疫人类供体的球蛋白亚中和稀释液与白细胞的组合，对致死性HSV感染具有高度保护作用。所涉及的细胞包括淋巴细胞或单核细胞 - 巨噬细胞。至少5×10⁶个活白细胞（或1×10⁶个单核细胞 - 巨噬细胞）以及低至10⁻⁸的免疫血清球蛋白浓度具有保护作用。感染细胞单层吸附和DEAE柱分级分离表明，球蛋白的保护作用归因于特异性抗病毒IgG抗体。在免疫转移前接受病毒的动物中未观察到保护作用。如体外实验所示，保护作用不涉及抗体和细胞的协同病毒中和作用。与正常幼鼠不同，接受球蛋白和细胞的动物具有循环抗病毒抗体和能够介导对HSV感染细胞进行ADCC的腹腔白细胞。这是人类ADCC作用的首个体内证据。该模型还允许对免疫受损人类的细胞抑制病毒感染的能力进行体内评估。
