Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones.
Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones.
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DOI：
10.4049/jimmunol.140.12.4245
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发表时间：
1988-06
影响因子：
4.4
通讯作者：
T. Gajewski;F. Fitch
中科院分区：
文献类型：
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作者：
T. Gajewski;F. Fitch
当IL-1依赖性HTL克隆D10暴露于IL-1加来自某些活化T细胞克隆而非其它克隆的上清液时，观察到双相剂量-反应曲线。基于以下发现，在这些上清液的高浓度下抑制增殖的活性组分似乎是IFN-γ：1）与上清液中IFN-γ的存在相关的双相应答模式; 2）抗IFN-γ mAb增强D10细胞对这些上清液的增殖;（3）rIFN-γ能显著抑制rIL-1+活化D10细胞上清或rIL-1 + rIL-4刺激的D10细胞反应;（4）rIFN-γ也能抑制D10细胞对rIL-1和rIL-2的反应，但抑制程度较低。用rIL-1加rIL-4或rIL-2刺激的另外的Th 2克隆的增殖也被rIFN-γ抑制，表明IFN-γ通常作为Th 2细胞的抑制性淋巴因子。rIFN-γ不影响两个Th 1克隆的增殖，也不影响非常规HTL克隆的增殖，所述非常规HTL克隆产生IL-4和IFN-γ，并且以IL-1非依赖性方式响应IL-2或IL-4而增殖。由Ag或固定化抗CD 3抗体刺激的D10细胞的增殖也被rIFN-γ阻断，而响应于这些刺激的IL-4产生不受影响，表明增殖而不是一般细胞功能被特异性抑制。总的来说，这些数据暗示IFN-γ作为HTL亚群（命名为Th 2）增殖的抑制因子，并表明在免疫应答期间存在的各种淋巴因子的相对量可能指导哪种T细胞类型的数量增加。
A biphasic dose-response curve was observed when the IL-1-dependent HTL clone D10 was exposed to IL-1 plus supernatants from some activated T cell clones but not others. The active component that inhibited proliferation at high concentrations of these supernatants appeared to be IFN-gamma based on the following findings: 1) the biphasic pattern of responsiveness correlated with the presence of IFN-gamma in the supernatants; 2) an anti-IFN-gamma mAb augmented the proliferation of D10 cells to these supernatants; 3) rIFN-gamma inhibited profoundly the response of D10 cells stimulated with rIL-1 plus supernatant from activated D10 cells or with rIL-1 plus rIL-4; 4) the response of D10 cells to rIL-1 plus rIL-2 also was inhibited by rIFN-gamma, although to a lesser extent. The proliferation of an additional Th2 clone stimulated with rIL-1 plus rIL-4 or rIL-2 also was inhibited by rIFN-gamma, implicating IFN-gamma as an inhibitory lymphokine for Th2 cells in general. rIFN-gamma did not affect the proliferation of two Th1 clones, nor did it affect the proliferation of an unconventional HTL clone which produces both IL-4 and IFN-gamma and proliferates in response to IL-2 or IL-4 in an IL-1-independent fashion. The proliferation of D10 cells stimulated by Ag or by immobilized anti-CD3 antibody also was blocked by rIFN-gamma, whereas IL-4 production in response to these stimuli was unaffected, indicating that proliferation and not general cell function was specifically inhibited. Collectively, these data implicate IFN-gamma as a suppressive factor for the proliferation of the subset of HTL designated Th2, and suggest that the relative amounts of the various lymphokines present during an immune response may direct which T cell types increase in number.