Lee T W, Kim M J
Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea.
Korean J Intern Med. 1992 Jan;7(1):31-8. doi: 10.3904/kjim.1992.7.1.31.
IL-2 production has been measured in several disease including type I diabetes mellitus, systemic lupus erythematosus, acquired immunodeficiency syndrome and active pulmonary sarcoidosis and its pathogenetic role was suggested. In IgA nephropathy, altered T cell subsets were reported to be associated with increased synthesis of IgA. The altered IL-2 production and the expression of IL-2 receptor might be involved in the pathogenesis of IgA nephropathy.
To investigate the role of T cell mediated immunity in the pathogenesis of IgA nephropathy, the immune parameters such as T cell subsets, NK cell activity, interleukin-2 (IL-2) production and IL-2 receptor expression on peripheral blood mononuclear cells (PBMC) were measured before and/or after phytohemagglutinin (PHA) stimulation in 15 patients with IgA nephropathy. Age and sex matched 15 healthy controls and the correlations between the IL-2 production and immune parameters were evaluated.
The mean percentages of T helper/inducer cells (CD4), T suppressor/cytotoxic cells (CD8) and the CD4/CD8 ratio of the patients were not different from those of controls and the proportions of CD8 CD11b cell in the patients (21.0 +/- 3.6%) were significantly lower than those in controls (30.5 +/- 5.3%) (p < 0.005). The production of IL-2 by fresh PBMC of both patients and controls was in undetectable ranges. The production of IL-2 by PHA stimulated PBMC of patients was significantly higher than that of controls (140.03 +/- 43.2 U/ml vs 106.5 +/- 42.1 U/ml, p < 0.05). The proportions of lymphocytes expressing the IL-2 receptor (CD25) before the stimulation with PHA in patients were 1.22 +/- 1.00 percent and were not different from those in controls (1.12 +/- 0.78 percent). The correlations between the production of IL-2 and the concentrations of serum IgA, the degrees of histologic alterations and the proportions of CD8 and CD8CD11b cells were not significant. There was a weak tendency of a positive correlation (p < 0.1) between the production of IL-2 and the proportions of CD4 cells, and the CD4/CD8 ratio showed a significant correlation with the production of IL-2 (p < 0.05). After PHA stimulation, the mean percentages of lymphocytes expressing the IL-2 receptors in patients were increased to 47.6 +/- 8.9 percents which is higher than those (40.4 +/- 9.9%) in controls (p < 0.05). The NK cell activity of the patients was higher than that of controls (75.6 +/- 19.6% vs 56.1 +/- 16.2%, p < 0.005), and was well correlated with the production of IL-2 by PBMC (r = 0.89, p < 0.05).
It seemed that patients with IgA nephropathy have an 'latent' cellular immunoregulatory dysfunction that becomes apparent on the stimulation of extrinsic antigens or mitogens.
白细胞介素 - 2（IL - 2）的产生已在多种疾病中进行了检测，包括I型糖尿病、系统性红斑狼疮、获得性免疫缺陷综合征和活动性肺结节病，并且提示了其发病机制中的作用。在IgA肾病中，据报道T细胞亚群的改变与IgA合成增加有关。IL - 2产生的改变和IL - 2受体的表达可能参与了IgA肾病的发病机制。
为了研究T细胞介导的免疫在IgA肾病发病机制中的作用，在15例IgA肾病患者中，于植物血凝素（PHA）刺激之前和/或之后，检测外周血单个核细胞（PBMC）上的免疫参数，如T细胞亚群、NK细胞活性、白细胞介素 - 2（IL - 2）产生和IL - 2受体表达。选取年龄和性别匹配的15名健康对照者，并评估IL - 2产生与免疫参数之间的相关性。
患者的辅助/诱导性T细胞（CD4）、抑制/细胞毒性T细胞（CD8）的平均百分比以及CD4/CD8比值与对照组无差异，患者中CD8⁺CD11b细胞的比例（21.0±3.6%）显著低于对照组（30.5±5.3%）（p<0.005）。患者和对照组新鲜PBMC产生的IL - 2均在检测不到的范围内。PHA刺激后患者PBMC产生的IL - 2显著高于对照组（140.03±43.2 U/ml对106.5±42.1 U/ml，p<0.05）。PHA刺激前患者中表达IL - 2受体（CD25）的淋巴细胞比例为1.22±1.00%，与对照组（1.12±0.78%）无差异。IL - 2产生与血清IgA浓度、组织学改变程度以及CD8和CD8⁺CD11b细胞比例之间的相关性不显著。IL - 2产生与CD4细胞比例之间存在弱的正相关趋势（p<0.1），并且CD4/CD8比值与IL - 2产生显示出显著相关性（p<0.05）。PHA刺激后，患者中表达IL - 2受体的淋巴细胞平均百分比增加至47.6±8.9%，高于对照组（40.4±9.9%）（p<0.05）。患者的NK细胞活性高于对照组（75.6±19.6%对56.1±16.2%，p<0.005），并且与PBMC产生的IL - 2密切相关（r = 0.89，p<0.05）。
似乎IgA肾病患者存在一种“潜在”的细胞免疫调节功能障碍，在外源性抗原或有丝分裂原刺激时变得明显。
