Ullum H, Gøtzsche P C, Victor J, Dickmeiss E, Skinhøj P, Pedersen B K
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
J Exp Med. 1995 Sep 1;182(3):789-99. doi: 10.1084/jem.182.3.789.
Cytotoxicity mediated by natural killer (NK) and lymphokine-activated killer (LAK) cells may be of significance in host defense against viral infections. This study included 347 patients infected with human immunodeficiency syndrome virus (HIV) type 1 and 110 controls. The NK cell activity, either unstimulated or stimulated with interferon-alpha (IFN-alpha) or interleukin-2 (IL-2), and the LAK cell activity were suppressed in patients, but the NK/LAK cell activity did not differ between patients with AIDS and patients without AIDS. However, the IFN-alpha-stimulated NK cell activity and LAK cell activity were reduced in patients with symptoms of HIV disease (CDCIV) when compared with asymptomatic patients (CDCII+III). When the data were analyzed by multiple linear regression, the percentage of CD4+ cells had a positive effect on these two parameters in patients without AIDS, whereas the percentage of CD4+ cells had no significant effect on unstimulated and IL-2-stimulated NK cell activity in these patients. In controls and AIDS patients, the percentage of CD4+ cells had no effect on NK/LAK cell activity in multiple linear models. The total number of CD16+ cells was low in patients compared to controls, whereas the percentages of CD16+, CD56+, and CD16+CD56+ were either normal or elevated. Therefore, the decrease in NK cell subpopulations did not contribute to the observed depression in NK/LAK cell activity in vitro. It is concluded that natural immunity is suppressed in HIV-seropositive patients primarily because of a qualitative defect of the NK/LAK cells. This qualitative defect includes a reduced responsiveness to IFN-alpha, which is progressive until the onset of symptoms, and possibly related to the loss of CD4+ cells.
自然杀伤（NK）细胞和淋巴因子激活的杀伤（LAK）细胞介导的细胞毒性在宿主抵御病毒感染中可能具有重要意义。本研究纳入了347例感染1型人类免疫缺陷病毒（HIV）的患者和110例对照。患者的NK细胞活性，无论是未刺激的还是用α干扰素（IFN-α）或白细胞介素-2（IL-2）刺激后的，以及LAK细胞活性均受到抑制，但艾滋病患者和非艾滋病患者的NK/LAK细胞活性并无差异。然而，与无症状患者（疾病控制与预防中心II + III期）相比，有HIV疾病症状（疾病控制与预防中心IV期）的患者中，IFN-α刺激的NK细胞活性和LAK细胞活性降低。当通过多元线性回归分析数据时，CD4 +细胞百分比对非艾滋病患者的这两个参数有正向影响，而CD4 +细胞百分比对这些患者未刺激的和IL-2刺激的NK细胞活性无显著影响。在对照和艾滋病患者中，CD4 +细胞百分比在多元线性模型中对NK/LAK细胞活性无影响。与对照相比，患者中CD16 +细胞总数较低，而CD16 +、CD56 +和CD16 + CD56 +的百分比要么正常要么升高。因此，NK细胞亚群的减少并非导致体外观察到的NK/LAK细胞活性降低的原因。结论是，HIV血清阳性患者的天然免疫受到抑制主要是由于NK/LAK细胞的质量缺陷。这种质量缺陷包括对IFN-α的反应性降低，这种降低在症状出现前呈进行性，并且可能与CD4 +细胞的丧失有关。
