Interleukin 2-induced proliferation of murine natural killer cells in vivo.
Interleukin 2-induced proliferation of murine natural killer cells in vivo.
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DOI：
10.1084/jem.171.1.173
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发表时间：
1990-01-01
期刊：
影响因子：
--
通讯作者：
Kasaian MT
中科院分区：
文献类型：
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作者：
Biron CA;Young HA;Kasaian MT
将生长因子IL-2给予小鼠以评价NK细胞对该因子的体内反应性。通过在用rIL-2单次处理后18-24小时检查细胞毒性活性来确定该因子对NK细胞的直接影响。虽然中等剂量的rIL-2（3 × 10（4）U）可以激活现有的细胞毒性细胞，在每个细胞的基础上，需要更高的剂量（10（6）U），以引发原始细胞大小的杀伤细胞。通过以下标准将引发的杀伤细胞表征为NK细胞：（a）它们容易在无胸腺小鼠中诱导;（B）它们介导NK敏感性YAC-1靶细胞的杀伤，但不介导NK抗性P815靶细胞的杀伤;以及（c）它们表达NK细胞决定簇脱唾液酸神经节苷脂-n-四糖神经酰胺和NK 1.1，但不表达T细胞决定簇CD 3、L3 T4或Lyt-2。高剂量IL-2处理不仅诱导原始大小NK细胞的出现，而且还诱导该群体的扩增。治疗后，大颗粒淋巴细胞的数量和NK 1.1+细胞的数量增加了至少两倍。NK1.1+细胞亚群内DNA含量的分析表明，IL-2优先驱动NK1.1+细胞进入细胞周期的S期和G2/M期。通过北方印迹分析和原位杂交检测体内诱导的原始淋巴细胞的IL-2-R p55 α链基因的表达。由于本实验室以前的工作已经证明NK细胞在体内响应IFN和IFN诱导剂而增殖，因此在IFN处理后也制备了原始淋巴细胞。在任何检查的条件下，NK细胞均未被诱导表达可检测水平的α链基因。诱导在病毒感染期间分离的原始T淋巴细胞转录α链基因，此时可以在体外证明IL-2的产生。用高剂量IL-2治疗正常胸腺小鼠也诱导41%的非B母细胞淋巴细胞中α链基因的转录，但只有背景百分比的NK 1.1+细胞表达α链基因。IL-2处理后，在NK细胞丰富的无胸腺小鼠中未诱导α链基因的转录。所有体内诱发的母细胞淋巴细胞均被诱导表达IFN-γ。综上所述，这些数据明确地证明IL-2可以在体内诱导NK细胞增殖和扩增。他们还表明，通过给予或内源性产生IL-2因子，体内暴露于IL-2可诱导含有T细胞亚群的细胞群中IL-2-R α链基因的转录。然而，结果表明，小鼠NK细胞在体内响应IL-2时不会被诱导表达高水平的α链基因。
The growth factor, IL-2, was administered to mice to evaluate the in vivo responsiveness of NK cells to this factor. The immediate effects of this factor on NK cells were determined by examining cytotoxic activity at 18-24 h after a single treatment with rIL-2. Although moderate doses of rIL-2 (3 x 10(4) U) could be shown to activate existing cytotoxic cells on a per cell basis, higher doses (10(6) U) were required to elicit blast size killer cells. The elicited killer cells were characterized as NK cells by the following criteria: (a) they were readily induced in athymic mice; (b) they mediated killing of NK-sensitive YAC-1 target cells but not NK-resistant P815 target cells; and (c) they expressed the NK cell determinants asialo ganglio-n- tetraosylceramide and NK1.1, but not the T cell determinants CD3, L3T4, or Lyt-2. High-dose IL-2 treatment induced not only the appearance of blast size NK cells, but also the expansion of this population. After treatments, the number of large granular lymphocytes and the number of NK1.1+ cells were increased at least twofold. Analysis of DNA content within the NK1.1+ cell subset demonstrated that IL-2 preferentially drove NK1.1+ cells into S and G2/M phases of the cell cycle. The in vivo elicited blast lymphocytes were examined by Northern blot analysis and in situ hybridization for expression of the IL-2-R p55 alpha chain gene. As previous work from this laboratory has demonstrated that NK cells proliferate in response to IFNs and IFN inducers in vivo, blast lymphocytes were also prepared after IFN treatments. The NK cells were not induced to express detectable levels of the alpha chain gene under any of the conditions examined. Blast T lymphocytes, isolated at times during viral infections when IL-2 production can be demonstrated in vitro, were induced to transcribe the alpha chain gene. Treatments of euthymic mice with high-dose IL-2 also induced transcription of the alpha chain gene in 41% of the non-B blast lymphocytes, but only background percentages of the NK1.1+ cells expressed the alpha chain gene. Transcription of the alpha chain gene was not induced in the NK cell-abundant athymic mice after IL-2 treatment. All of the in vivo elicited blast lymphocytes were induced to express IFN-gamma. Taken together, these data definitively demonstrate that IL-2 can induce NK cell proliferation and expansion in vivo. They also show that exposure to IL-2 in vivo, either by administration or endogenous production of the factor, induces transcription of the IL-2-R alpha chain gene in populations of cells containing T cell subsets. The results suggest, however, that murine NK cells are not induced to express high levels of the alpha chain gene in response to IL-2 in vivo.