Lai K N, Ho R T, Lai C K, Chan C H, Li P K
Department of Medicine, Prince of Wales Hospital, Chinese University of Hong Kong.
Clin Exp Immunol. 1994 Apr;96(1):116-21. doi: 10.1111/j.1365-2249.1994.tb06240.x.
IgA nephropathy (IgAN), characterized by glomerular deposition of IgA and frequently elevated plasma IgA levels, has increased T helper cell activity. In vitro measurement of cytokines in supernatant of cultured peripheral lymphocytes revealed conflicting findings. We examined the profile of cytokine mRNA expressed in purified CD4+ cells in patients with IgAN in order to study their pattern of Th1 (releases IL-2 and interferon-gamma (IFN-gamma)) and Th2 (releases IL-4 and IL-5) T cell response. We assessed the circulating CD4+ T cells in patients and normal controls by the expression of messenger RNA (mRNA) for IL-2, IL-4, IL-5 and IFN-gamma. The cytokine mRNAs were analysed with reverse transcription-polymerase chain reaction and were measured semiquantitatively by using a housekeeping gene, beta-actin. Compared with the control subjects, CD4+ T lymphocytes from patients with IgAN expressed a higher level of IL-2 mRNA (P = 0.007), IFN-gamma mRNA (P = 0.04), IL-4 mRNA (P = 0.048), and IL-5 mRNA (P = 0.016). Within these patients with IgAN, a good correlation was demonstrated between the gene expression of cytokines in Th1 or Th2 cells. The IL-2 mRNA levels in Th1 cells from these patients with IgAN also correlated significantly with the IL-4 or IL-5 mRNA levels in their Th2 cells. Our study revealed IgAN is associated with activation in circulating lymphocytes of the IL-2, IFN-gamma, IL-4 and IL-5 gene cluster, a pattern compatible with activation of both the Th1- and Th2-like T lymphocyte population. The increased transcription of these cytokines genes may be contributory to the immunopathologic findings in IgAN.
IgA肾病(IgAN)以肾小球IgA沉积和血浆IgA水平频繁升高为特征,其辅助性T细胞活性增强。体外测量培养的外周淋巴细胞上清液中的细胞因子得出了相互矛盾的结果。我们检测了IgAN患者纯化的CD4+细胞中表达的细胞因子mRNA谱,以研究其Th1(释放白细胞介素-2(IL-2)和干扰素-γ(IFN-γ))和Th2(释放IL-4和IL-5)T细胞反应模式。我们通过检测IL-2、IL-4、IL-5和IFN-γ的信使RNA(mRNA)表达来评估患者和正常对照中的循环CD4+T细胞。采用逆转录-聚合酶链反应分析细胞因子mRNA,并使用管家基因β-肌动蛋白进行半定量测定。与对照组相比,IgAN患者的CD4+T淋巴细胞表达的IL-2 mRNA水平更高(P = 0.007)、IFN-γ mRNA水平更高(P = 0.04)、IL-4 mRNA水平更高(P = 0.048)以及IL-5 mRNA水平更高(P = 0.016)。在这些IgAN患者中,Th1或Th2细胞中细胞因子的基因表达之间显示出良好的相关性。这些IgAN患者Th1细胞中的IL-2 mRNA水平也与Th2细胞中的IL-4或IL-5 mRNA水平显著相关。我们的研究表明,IgAN与IL-2、IFN-γ、IL-4和IL-5基因簇的循环淋巴细胞激活有关,这种模式与Th1样和Th2样T淋巴细胞群体的激活均相符。这些细胞因子基因转录的增加可能是IgAN免疫病理表现的原因。