Welsh R M
J Exp Med. 1978 Jul 1;148(1):163-81. doi: 10.1084/jem.148.1.163.
Lymphocytic choriomeningitis virus (LCMV) infection of C3H/St, nude (BALB/c background), and other mice induced high levels of natural killer (NK) cell activity in the spleen and peritoneum. L-929 cells were used as targetsand were not lysed by spleen or peritoneal cells from uninfected mice. The cytotoxic cells were characterized as NK cells because they were nonadherent, nonphagocytic lymphocytes lacking theta and immunoglobulin antigens on their plasma membranes. Their activity was sensitive to 6 mM EDTA and to heating for 5 h at 37 degrees C, but resisted treatment with 0.5 percent trypsin. No role for antibody could be demonstrated in these assays. Relative to cytotoxic T-cell activity, the induction of NK cell activity was resistant to X-irradiation of mice with 1,000 rads but was sensitive if mice were first treated with Strontium-89, a bone-seeking isotope. NK cells were induced by LCMV in all tested strains of mice. In C3H/St mice NK cell activity was detected as early as 1 day and peaked at 3 days postinfection. Maximum activity in C3H/St mice was observed in mice 5-10 wk of age, but significant NK activity was also induced in newborns, which subsequently carried virus in their tissues for the duration of their lives. Older LCMV-carriers did not have detectable spleen NK cell activity. No memory oranamnestic response could be demonstrated for NK cell induction. NK cell activity was not induced by LCMV challenge of LCMV-immune mice, but was induced in those mice by infection with Pichinde virus, a closely related virus. The advent of NK cell activity correlated with the synthesis of interferon in LCMV-infected mice. Culture fluids lacking virus infectivity but containing interferon induced cytotoxic cell activity in nude and C3H/St mice. These experiments suggest that LCMV induced NK cells via an interferon-dependent mechanism. When studied in several strains of mice, the continued expression of NK cell activity did not seem to directly correlate with spleen interferon levels, suggesting that additional factors may play a role as well in maintaining the activity of the NK cell in vivo.
淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染C3H/St小鼠、裸鼠（BALB/c背景）及其他品系小鼠后，可诱导脾脏和腹膜中自然杀伤（NK）细胞活性显著升高。以L-929细胞作为靶细胞，未感染小鼠的脾脏或腹膜细胞不能将其裂解。这些细胞毒性细胞被鉴定为NK细胞，因为它们是非黏附性、非吞噬性淋巴细胞，其细胞膜上缺乏θ和免疫球蛋白抗原物质。它们的活性对6 mM的EDTA以及在37℃加热5小时敏感，但对0.5%的胰蛋白酶处理有抗性。在这些实验中未证实抗体发挥作用。相对于细胞毒性T细胞活性，NK细胞活性的诱导对1000拉德的X射线照射有抗性，但如果先用亲骨性同位素锶-89处理小鼠，则会变得敏感。在所有测试品系的小鼠中，LCMV均可诱导NK细胞产生。在C3H/St小鼠中，感染后最早在第1天即可检测到NK细胞活性，并在第3天达到峰值。C3H/St小鼠在5至10周龄时NK细胞活性最高，但新生小鼠也可诱导出显著的NK活性，这些新生小鼠随后在其组织中终生携带病毒。年龄较大的LCMV携带者脾脏中未检测到NK细胞活性。未证实NK细胞诱导存在记忆或回忆反应。LCMV免疫小鼠经LCMV攻击后未诱导出NK细胞活性，但感染密切相关的皮钦德病毒可诱导这些小鼠产生NK细胞活性。NK细胞活性的出现与LCMV感染小鼠中干扰素的合成相关。缺乏病毒感染性但含有干扰素的培养液可在裸鼠和C3H/St小鼠中诱导细胞毒性细胞活性。这些实验表明，LCMV通过干扰素依赖性机制诱导NK细胞产生。在多个品系小鼠中进行研究时，NK细胞活性的持续表达似乎与脾脏干扰素水平无直接关联，这表明可能还有其他因素在体内维持NK细胞活性方面发挥作用。
