Klein S A, Dobmeyer J M, Dobmeyer T S, Pape M, Ottmann O G, Helm E B, Hoelzer D, Rossol R
Medical Clinic III, Johann Wolfgang Goethe University, Frankfurt, Germany.
AIDS. 1997 Jul 15;11(9):1111-8. doi: 10.1097/00002030-199709000-00005.
To characterize changes of Th1/Th2 cytokine production by peripheral blood mononuclear cells (PBMC) that occur during the course of HIV infection by cytoplasmic cytokine staining on single cell level.
Mitogen-stimulated PBMC from 16 healthy donors, 18 HIV-1-infected individuals without AIDS and 14 patients with AIDS were stained intracellularly with fluorescein-labelled MAb against interleukin (IL)-2, IL-4, IL-10 and interferon (IFN)-gamma. Additionally, co-staining of CD4+ T-cell, CD8+ T-cell, natural killer (NK) cell, B-cell and monocytic markers was performed. Fluorescence staining was analysed by three-colour flow-cytometry.
A reduced percentage of IL-2 and IFN-gamma (Th1 type)-producing cells among CD4+ T cells from HIV-1-infected individuals could be demonstrated. There was a continuous decrease of IFN-gamma-producing CD4+ T cells in the course of HIV infection and a dramatic reduction of IL-2-expressing cells among CD4+ T cells in patients with AIDS. In contrast to Th1 cytokines, the frequency of Th2 cytokine expressing cells among CD4+ T cells increased in HIV-infected individuals. The maximum frequency of IL-4-expressing cells among CD4+ T cells was seen in HIV-infected individuals without AIDS, whereas the rate of IL-10-producing cells was highest in patients with AIDS. In HIV-infected individuals no significant proportion of Th0 cells expressing both Th1 and Th2 cytokines was detectable. In CD8+ T cells the percentage of IL-2 was expressing cells decreased continuously accompanied by a strong increase of the frequency of IFN-gamma-producing cells.
The decreased percentage of cells expressing IL-2 and IFN-gamma in conjunction with an increased proportion of IL-4- and IL-10-producing cells among the CD4+ T cells in HIV-1-infected individuals demonstrate a Th1 to Th2 cytokine shift in the course of HIV infection on a single cell level. There was no evidence of a Th1 to Th0 cytokine shift. In addition to the loss of CD4+ T cells in HIV infection, the qualitative changes of Th1/Th2 cytokine expression may serve as a marker for progressive failure of cell-mediated immunity.
通过单细胞水平的细胞质细胞因子染色来描述HIV感染过程中外周血单个核细胞（PBMC）产生的Th1/Th2细胞因子的变化。
用荧光素标记的抗白细胞介素（IL）-2、IL-4、IL-10和干扰素（IFN）-γ单克隆抗体对来自16名健康供体、18名未患艾滋病的HIV-1感染者和14名艾滋病患者的丝裂原刺激的PBMC进行细胞内染色。此外，还进行了CD4⁺ T细胞、CD8⁺ T细胞、自然杀伤（NK）细胞、B细胞和单核细胞标志物的共染色。通过三色流式细胞术分析荧光染色。
可以证明HIV-1感染者的CD4⁺ T细胞中产生IL-2和IFN-γ（Th1型）的细胞百分比降低。在HIV感染过程中，产生IFN-γ的CD4⁺ T细胞持续减少，而艾滋病患者的CD4⁺ T细胞中表达IL-2的细胞急剧减少。与Th1细胞因子相反，HIV感染者的CD4⁺ T细胞中表达Th2细胞因子的细胞频率增加。CD4⁺ T细胞中表达IL-4的细胞的最高频率出现在未患艾滋病的HIV感染者中，而产生IL-10的细胞比例在艾滋病患者中最高。在HIV感染者中，未检测到同时表达Th1和Th2细胞因子的Th0细胞的显著比例。在CD8⁺ T细胞中，表达IL-2的细胞百分比持续下降，同时产生IFN-γ的细胞频率大幅增加。
HIV-1感染者的CD4⁺ T细胞中表达IL-2和IFN-γ的细胞百分比降低，同时产生IL-4和IL-10的细胞比例增加，这表明在HIV感染过程中，在单细胞水平上发生了从Th1细胞因子向Th2细胞因子的转变。没有证据表明存在从Th1细胞因子向Th0细胞因子的转变。除了HIV感染中CD4⁺ T细胞的损失外，Th1/Th2细胞因子表达的定性变化可能作为细胞介导免疫进行性衰竭的标志物。
