Interleukin 2 enhances the natural killer cell activity of acquired immunodeficiency syndrome patients through a gamma-interferon-independent mechanism.
Interleukin 2 enhances the natural killer cell activity of acquired immunodeficiency syndrome patients through a gamma-interferon-independent mechanism.
复制标题
白细胞介素 2 通过不依赖 γ 干扰素的机制增强获得性免疫缺陷综合征患者的自然杀伤细胞活性。
作者：
A. Rook;J. Hooks;G. Quinnan,;H. Lane;J. Manischewitz;A. Macher;H. Masur;A. Fauci;J. Djeu
获得性免疫缺陷综合征（AIDS）患者表现出多种细胞免疫紊乱，包括产生细胞毒性T细胞的能力不足和自然杀伤（NK）细胞活性水平降低。白细胞介素2（IL 2）在体外可明显增强这些受抑制的免疫功能。由于IL-2可诱导正常外周血淋巴细胞（PBL）释放干扰素-γ（IFN-γ），且IFN-γ可能在调节NK细胞活性中起作用，因此本研究旨在确定IL-2增强AIDS患者NK细胞活性是否为IFN-γ依赖性效应。研究了来自8名健康异性供者和9名艾滋病患者的PBL对浓度为100 U/ml的IL-2的反应释放IFN-γ的能力。培养60小时后，所有8名健康供体的PBL产生平均滴度为113 U/ml（范围为40至320 U/ml）的IFN-γ。相比之下，9名AIDS患者中只有2名患者的PBL释放可测量量的IFN-γ（各40 U/ml）以响应IL 2，所有9名患者的平均滴度为13.5 U/ml。尽管来自AIDS患者的PBL对100 U/ml的IL-2产生IFN-γ的能力不足，但用10 U/ml的IL-2处理PBL仅1小时就可获得显著的NK细胞活性增强，其中最佳NK增强效应发生在50至100 U/ml的IL-2剂量下。抗IFN-γ单克隆抗体的使用导致从与IL 2培养的正常PBL释放的IFN被完全中和，但未能抑制IL 2对NK细胞活性的增强。与IL 2相比，外源性IFN-γ表现出不同的NK细胞活性增强动力学，需要基本上超过1小时的PBL预处理。这些结果表明，从艾滋病患者的PBL通常不释放IFN-γ时，与IL-2培养，IL-2增强这些患者的NK细胞活性下降可能是一个IFN-γ非依赖性事件。这些结果可能对艾滋病的治疗具有重要意义。
Patients with the acquired immunodeficiency syndrome (AIDS) exhibit a variety of disorders of cellular immunity, including a deficient ability to generate cytotoxic T cells and depressed levels of natural killer (NK) cell activity. Interleukin 2 (IL 2) in vitro can markedly augment these depressed immune functions. Because IL 2 can induce the release of interferon-gamma (IFN-gamma) from normal peripheral blood lymphocytes (PBL), and because IFN-gamma may play a role in the regulation of NK cell activity, this study was performed to determine if the IL 2 enhancement of the NK cell activity of patients with AIDS was an IFN-gamma-dependent effect. PBL from eight healthy heterosexual donors and from nine patients with AIDS were studied for their ability to release IFN-gamma in response to IL 2 at a concentration of 100 U/ml. After 60 hr of culture, the PBL of all eight healthy donors produced IFN-gamma with a mean titer of 113 U/ml (range 40 to 320 U/ml). In contrast, the PBL from only two of nine patients with AIDS released measurable amounts of IFN-gamma (40 U/ml each) in response to IL 2 with a mean titer of 13.5 U/ml for all nine. Although the PBL from patients with AIDS were deficient in their capacity to produce IFN-gamma in response to 100 U/ml of IL 2, significant enhancement of NK cell activity could be obtained after only 1 hr of PBL treatment with 10 U/ml of IL 2, with an optimal NK enhancing effect occurring at doses of 50 to 100 U/ml of IL 2. The use of an anti-IFN-gamma monoclonal antibody resulted in complete neutralization of the IFN released from the normal PBL cultured with IL 2, but failed to inhibit the IL 2 enhancement of NK cell activity. Exogenous IFN-gamma exhibited different kinetics of enhancement of NK cell activity when compared to IL 2, requiring substantially more than 1 hr of pretreatment of PBL. These results indicate that the PBL from patients with AIDS usually do not release IFN-gamma when cultured with IL 2, and that IL 2 enhancement of the depressed NK cell activity of these patients may be an IFN-gamma-independent event. These results may have important implications for the therapy of AIDS.