Interleukin-10 reduces natural killer sensitivity and downregulates MHC class I expression on H-ras-transformed cells.
Interleukin-10 reduces natural killer sensitivity and downregulates MHC class I expression on H-ras-transformed cells.
复制标题
Interleukin-10 降低自然杀伤细胞敏感性并下调 H-ras 转化细胞上 MHC I 类表达。
作者：
T. Tsuruma;A. Yagihashi;T. Torigoe;N. Sato;K. Kikuchi;N. Watanabe;K. Hirata
我们研究了IL-10对H-ras诱导的转化体W14和W31对NK细胞介导的细胞毒性的敏感性的影响。与重组人（rh）IL-10的细胞孵育导致剂量依赖性减少的MHC I类抗原的表达，但不是在ICAM-1的表达。然而，预先孵育W31细胞与rhIL-10显着降低其对大鼠脾NK细胞的细胞溶解的敏感性。这一事实表明，IL-10介导的MHC I类表达的减少可能并不主导NK敏感性的调节。当大鼠IL-10 cDNA导入的W31细胞用作内源性IL-10产生者时，这是真实的。IL-10高表达克隆W31 T-H的体外NK敏感性被抑制至与外源性rhIL-10预处理的W31细胞相当的水平。体内Winn试验进一步证实了W31 T-H细胞NK敏感性的降低，其中用W31 T-H细胞和大鼠NK细胞攻击的裸鼠一起产生肿瘤，而用W31 T-L（最小IL-10产生克隆）和NK细胞攻击的裸鼠没有。由于外源性和内源性IL-10均不影响W31细胞的增殖，因此数据表明W31 T-H细胞可以逃避体内NK细胞介导的免疫应答。总之，我们的数据揭示了一种新的机制，IL-10介导的逃逸肿瘤细胞从宿主免疫系统的NK细胞。
We examined the effect of IL-10 on sensitivity to NK-cell-mediated cytotoxicity of the H-ras-induced transformants, W14 and W31. Incubation of cells with recombinant human (rh) IL-10 resulted in a dose-dependent decrease in the expression of MHC class I antigens, but not in the ICAM-1 expression. However, prior incubation of W31 cells with rhIL-10 markedly decreased their susceptibility to cytolysis by rat splenic NK cells. This fact suggested that the IL-10-mediated decrease in MHC class I expression might not dominate the regulation of the NK sensitivity. This was true when rat IL-10 cDNA-introduced W31 cells were used as an endogenous IL-10 producer. The NK sensitivity in vitro of W31T-H, a high IL-10-producer clone, was suppressed downward to the equivalent level of W31 cells pretreated with exogenous rhIL-10. The decreased NK-sensitivity of W31T-H cells was further confirmed by in vivo Winn assay, in which nude mice challenged with W31T-H cells and rat NK cells together developed tumors, whereas nude mice challenged with W31T-L, a minimal-IL-10 producer clone, and NK cells did not. Since neither exogenous nor endogenous IL-10 affected the proliferation of W31 cells, the data indicated that W31T-H cells could evade the NK-cell-mediated immune response in vivo. Taken together, our data reveal a novel mechanism for an IL-10-mediated escape of tumor cells from host immune system by NK cells.
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DOI：
--
发表时间：
1990
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
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影响因子：
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影响因子：
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作者：
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作者：
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作者：
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