Fan J, Bass H Z, Fahey J L
Center for Interdisciplinary Research in Immunology and Diseases, University of California, Los Angeles School of Medicine 90024-1747.
J Immunol. 1993 Nov 1;151(9):5031-40.
Because cytokines have a central role in the regulation and function of the human immune system, expression of several key cytokine genes in HIV infection was compared by quantitative polymerase chain reaction studies in lymphocytes from HIV-seronegative and -seropositive subjects. Elevated levels of IFN-gamma mRNA and lowered IL-2 mRNA were found in the PBMC of eight seropositive men with CD4 T cells over 500/mm3 (mean, 647/mm3), whereas IL-4 and IL-10 mRNA were not changed significantly. PBMC obtained 2 yr later from four of these patients with stable disease status (unchanged CD4 T cell number) showed median mRNA levels that were nearer normal for IFN-gamma and for IL-2. Four other men whose CD4 levels fell more than 200/mm3 in the following 2 yr, however, showed increased IFN-gamma and lowered IL-2. Purified CD4 and CD8 T cells from 10 HIV-seropositive and 10 -seronegative homosexual men were compared. Cytokine gene expression was found to be markedly different in CD4 and CD8 T cells from HIV-seropositive men. In CD8 T cells on a per-cell basis, the levels of cytokine mRNA were substantially lower than in CD4 T cells and were not markedly changed in HIV infection. In the CD4 T cells, on a per-cell basis, the mean mRNA levels of IFN-gamma, IL-10, and TNF-alpha were increased substantially (p < 0.001) in HIV infection. IL-2 gene expression was not increased significantly. Thus, the low IL-2 mRNA expression seen in PBMC is primarily due to the reduced CD4 T cell numbers. Increased expression of IFN-gamma genes in CD4 T cells, however, indicates that these cells may be responsible for substantial amounts of circulating IFN-gamma that occur in HIV infection. The striking difference in the effect of HIV infection on the expression of IFN-gamma and IL-2 genes indicates that these cytokines are under separate control. IL-4 mRNA levels were not changed. IL-10 gene expression, however, was increased more in early HIV infection, with less of an increase later. Expression of all cytokines in CD4 T cells appeared to subside late in HIV infection. However, the balance of cytokine expression was altered in all stages of HIV infection.
由于细胞因子在人类免疫系统的调节和功能中起着核心作用，因此通过定量聚合酶链反应研究，比较了HIV血清阴性和血清阳性受试者淋巴细胞中几种关键细胞因子基因的表达。在8名CD4 T细胞计数超过500/mm3（平均647/mm3）的血清阳性男性的外周血单核细胞（PBMC）中，发现IFN-γ mRNA水平升高而IL-2 mRNA水平降低，而IL-4和IL-10 mRNA没有明显变化。2年后从其中4名疾病状态稳定（CD4 T细胞数量未改变）的患者获取的PBMC显示，IFN-γ和IL-2的mRNA水平中位数更接近正常水平。然而，另外4名男性在接下来的2年中CD4水平下降超过200/mm3，他们的IFN-γ水平升高而IL-2水平降低。比较了10名HIV血清阳性和10名血清阴性同性恋男性的纯化CD4和CD8 T细胞。发现HIV血清阳性男性的CD4和CD8 T细胞中细胞因子基因表达存在显著差异。以每个细胞为基础，HIV血清阳性男性的CD8 T细胞中细胞因子mRNA水平显著低于CD4 T细胞，并且在HIV感染中没有明显变化。在CD4 T细胞中，以每个细胞为基础，HIV感染时IFN-γ、IL-10和TNF-α的平均mRNA水平显著升高（p < 0.001）。IL-2基因表达没有显著增加。因此，PBMC中观察到的低IL-2 mRNA表达主要是由于CD4 T细胞数量减少。然而，CD4 T细胞中IFN-γ基因表达增加表明，这些细胞可能是HIV感染中循环IFN-γ的主要来源。HIV感染对IFN-γ和IL-2基因表达的影响存在显著差异，表明这些细胞因子受不同的调控。IL-4 mRNA水平没有变化。然而，IL-10基因表达在HIV感染早期增加更多，后期增加较少。CD4 T细胞中所有细胞因子的表达在HIV感染后期似乎都有所下降。然而，HIV感染的各个阶段细胞因子表达的平衡都发生了改变。
