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全身性体内白细胞介素-2(IL-2)重建对获得性免疫缺陷综合征(AIDS)和艾滋病相关综合征(ARC)患者外周血单个核细胞(PBMC)表型及功能的影响

Effects of systemic in vivo interleukin-2 (IL-2) reconstitution in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) on phenotypes and functions of peripheral blood mononuclear cells (PBMC).

作者信息

Ernst M, Kern P, Flad H D, Ulmer A J

出版信息

J Clin Immunol. 1986 Mar;6(2):170-81. doi: 10.1007/BF00918750.

Abstract

In the context of a clinical phase I/II therapy study with recombinant interleukin-2 (rIL-2), we monitored immunological alterations in four patients with acquired immune deficiency syndrome (AIDS) and three patients with AIDS-related complex (ARC). By determining the surface phenotypes and in vitro functions of peripheral blood mononuclear cells (PBMC) before, during, and after treatment with rIL-2, we observed transient changes in all important leukocyte subpopulations, a minor restoration of immune reactivity in vitro, and an improvement in skin reactivity in vivo. In particular, we found a transient increase in C3b receptor-mediated monocyte activation in ARC patients; no influence of therapy on the otherwise intact LPS-induced interleukin-1 production in vitro; in some patients a transient corrective influence on the high pretherapeutic immunoglobulin secretion of B cells and their nonresponsiveness to pokeweed mitogen; low T-cell responses to soluble antigens and alloantigens, which were partially restored during rIL-2 treatment in ARC patients and in one AIDS patient; defective NK activity in PBMC of two AIDS patients, which was found to be restored when measured at the end of rIL-2 therapy; and a rather constant phenotypic pattern of PBMC in each patient during therapy except for the decreasing proportion of OKT9-positive lymphocytes in AIDS patients, the increasing proportion of Leu8-Leu3a+ lymphocytes in all patients, and in particular, the transient significant decrease in the Leu7+/OKT3+ ratio, which pretherapeutically was very high in AIDS patients (0.78 +/- 0.21) and high in ARC patients (0.48 +/- 0.06) as compared to healthy controls (0.18 +/- 0.08).

摘要

在一项使用重组白细胞介素-2(rIL-2)的临床I/II期治疗研究中,我们监测了4例获得性免疫缺陷综合征(AIDS)患者和3例AIDS相关综合征(ARC)患者的免疫变化。通过测定外周血单个核细胞(PBMC)在rIL-2治疗前、治疗期间和治疗后的表面表型及体外功能,我们观察到所有重要白细胞亚群均有短暂变化,体外免疫反应有轻微恢复,体内皮肤反应性有所改善。具体而言,我们发现ARC患者中C3b受体介导的单核细胞活化有短暂增加;治疗对体外原本完整的脂多糖诱导的白细胞介素-1产生无影响;在一些患者中,对治疗前B细胞高免疫球蛋白分泌及其对商陆有丝分裂原无反应有短暂的纠正作用;T细胞对可溶性抗原和同种异体抗原的反应较低,在ARC患者和1例AIDS患者的rIL-2治疗期间部分恢复;2例AIDS患者PBMC中的自然杀伤(NK)活性缺陷,在rIL-2治疗结束时测定发现其恢复;除AIDS患者中OKT9阳性淋巴细胞比例下降、所有患者中Leu8-Leu3a +淋巴细胞比例增加外,尤其是Leu7 + /OKT3 +比值短暂显著下降,治疗前该比值在AIDS患者中非常高(0.78±0.21),在ARC患者中较高(0.48±0.06),而在健康对照中较低(0.18±0.08),每位患者在治疗期间PBMC的表型模式相当稳定。

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