Takagi M, Koike K, Nakahata T
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
J Immunol. 1990 Sep 15;145(6):1880-4.
Mouse rIFN-gamma suppressed clonal growth of tissue-type mast cells (CTMC) separated from mouse peritoneal cells (greater than or equal to 98% purity) in methylcellulose culture containing IL-3 + IL-4 in a dose-dependent fashion. The IFN-gamma-mediated suppression was also observed both in serum-free culture and in single-cell culture. In addition, mAb to mouse IFN-gamma neutralized the suppressive effect of IFN-gamma on CTMC proliferation supported by the combination of IL-3 + IL-4. These observations suggest a direct antiproliferative effect of IFN-gamma on CTMC. No suppression of CTMC proliferation was observed when CTMC were washed with alpha-medium after 24 h of preincubation with IL-3 + IFN-gamma and then cultured in methylcellulose medium containing IL-3 + IL-4. IFN-gamma had suppressive effects on CTMC after preincubation with IL-3 + IL-4. These preincubation studies suggest that IFN-gamma exerts a reversible inhibitory effect on CTMC which have entered into a proliferative state by IL-3 + IL-4, and has neither cytotoxic nor irreversible suppressive effects on resting CTMC in cultures containing IL-3 alone. CTMC proliferation after stimulation with the cross-linking of cell-bound IgE by specific Ag in the presence of IL-3 was also suppressed by IFN-gamma. By contrast, proliferation of CTMC induced by the combination of 12-O-tetradecanoyl phorbol-13-acetate + IL-3 was not affected by the addition of IFN-gamma to the culture. Based on these observations, we suggest that IFN-gamma antagonizes the colony inducing effect of IL-4 and IgE-Ag stimulation which act synergistically with IL-3 on CTMC.
小鼠重组干扰素-γ（rIFN-γ）在含有白细胞介素-3（IL-3）+白细胞介素-4（IL-4）的甲基纤维素培养基中，以剂量依赖的方式抑制从小鼠腹腔细胞分离的组织型肥大细胞（CTMC，纯度大于或等于98%）的克隆生长。在无血清培养和单细胞培养中也观察到了干扰素-γ介导的抑制作用。此外，抗小鼠干扰素-γ单克隆抗体中和了干扰素-γ对由IL-3 + IL-4组合支持的CTMC增殖的抑制作用。这些观察结果表明干扰素-γ对CTMC具有直接的抗增殖作用。当CTMC在与IL-3 +干扰素-γ预孵育24小时后用α-培养基洗涤，然后在含有IL-3 + IL-4的甲基纤维素培养基中培养时，未观察到CTMC增殖受到抑制。干扰素-γ在与IL-3 + IL-4预孵育后对CTMC有抑制作用。这些预孵育研究表明，干扰素-γ对已通过IL-3 + IL-4进入增殖状态的CTMC发挥可逆的抑制作用，而对仅含IL-3的培养物中的静止CTMC既无细胞毒性作用也无不可逆的抑制作用。在IL-3存在的情况下，特异性抗原使细胞结合的IgE交联刺激后CTMC的增殖也受到干扰素-γ的抑制。相比之下，向培养物中添加干扰素-γ并不影响由12-氧-十四烷酰佛波醇-13-乙酸酯+ IL-3组合诱导的CTMC增殖。基于这些观察结果，我们认为干扰素-γ拮抗IL-4和IgE-抗原刺激的集落诱导作用，IL-4和IgE-抗原刺激与IL-3协同作用于CTMC。
