Beck M A, Sheridan J F
Department of Medical Microbiology, College of Medicine, Ohio State University, Columbus 43210.
J Immunol. 1989 May 15;142(10):3560-7.
Mononuclear cells, obtained from the spleens and lungs of influenza virus-seropositive C57BL/6 mice at 2 to 4 days after re-infection with homologous virus (strain A/Bangkok/1/79), produced a low m.w. factor in vitro that prevents the biologic expression, but not production, of the lymphokine, leukocyte migration inhibition factor (LIF). The low m.w. factor inhibited LIF activity without destroying the LIF molecule inasmuch as simple dialysis restored lymphokine activity to culture supernatants. Production of the low m.w. factor was observed from 2 to 4 days after re-infection, at which time the delayed-type hypersensitivity response to viral Ag was suppressed. In contrast, LIF was produced by splenocytes and lung mononuclear cells obtained at all times tested after re-infection (from 2 to 30 days). Production of the low m.w. factor required re-infection of influenza A virus-seropositive mice with type A virus; re-infection with influenza B virus failed to induce production. Ag specificity was also required in vitro for splenocytes to produce the factor; cells from type A virus-re-infected mice required type A Ag stimulation. Cell depletion studies with mAb plus C revealed that macrophages and T cells along with Ag stimulation were required for factor production by spleen cells. However, mononuclear cells obtained within 4 days from the lungs of re-infected mice did not require in vitro Ag stimulation for production of the low m.w. factor, and factor production was dependent upon the presence of CD4+ (L3T4) cells in the culture. Fractionation of culture supernatants over a Sephadex G-50 column indicated that the factor had a molecular mass of 2 to 3 kDa, and by FPLC chromatofocusing over a Mono P column, the factor eluted at a pH of approximately 8.2. Thus, re-exposure of influenza virus-seropositive mice to homologous virus resulted in the production of a low m.w. factor that prevented the biologic expression of LIF, but not its production. Lymphokines are an important component of the delayed-type hypersensitivity response; the presence of mononuclear cells secreting a low m.w. factor and LIF concomitantly at the site of virus replication (lungs) and the capacity of the factor to block the biologic expression of LIF in vitro suggest that the factor may have a role in the regulation of a delayed-type hypersensitivity response in vivo during re-infection.
从再次感染同源病毒（A/曼谷/1/79株）2至4天后的流感病毒血清阳性C57BL/6小鼠的脾脏和肺中获取的单核细胞，在体外产生了一种低分子量因子，该因子可阻止淋巴因子白细胞迁移抑制因子（LIF）的生物学表达，但不影响其产生。低分子量因子抑制了LIF活性，但未破坏LIF分子，因为简单透析可使培养上清液恢复淋巴因子活性。在再次感染后2至4天观察到低分子量因子的产生，此时对病毒抗原的迟发型超敏反应受到抑制。相比之下，在再次感染后的所有测试时间（2至30天）从脾脏细胞和肺单核细胞中均产生了LIF。低分子量因子的产生需要甲型流感病毒血清阳性小鼠再次感染甲型病毒；再次感染乙型流感病毒未能诱导产生。体外脾细胞产生该因子也需要抗原特异性；来自再次感染甲型病毒小鼠的细胞需要甲型抗原刺激。用单克隆抗体加补体进行细胞清除研究表明，脾细胞产生该因子需要巨噬细胞、T细胞以及抗原刺激。然而，从再次感染小鼠的肺中在4天内获取的单核细胞产生低分子量因子不需要体外抗原刺激，且因子产生依赖于培养物中CD4+（L3T4）细胞的存在。在Sephadex G - 50柱上对培养上清液进行分级分离表明该因子的分子量为2至3 kDa，通过在Mono P柱上进行快速蛋白质液相色谱聚焦，该因子在pH约为8.2时洗脱。因此，流感病毒血清阳性小鼠再次暴露于同源病毒导致产生一种低分子量因子，该因子可阻止LIF的生物学表达，但不影响其产生。淋巴因子是迟发型超敏反应的重要组成部分；在病毒复制部位（肺）同时存在分泌低分子量因子和LIF的单核细胞，以及该因子在体外阻断LIF生物学表达的能力表明，该因子可能在再次感染期间体内迟发型超敏反应的调节中发挥作用。
