Production of Interleukin-2 (IL-2) and Expression of IL-2 Receptor in Patients with IgA Nephropathy

BACKGROUND: IL-2 production has been measured in several disease including type I diabetes mellitus(9)), systemic lupus erythematosus(10,11)), acquired immunodeficiency syndrome(12,13)) and active pulmonary sarcoidosis(14)) and its pathogenetic role was suggested. In IgA nephropathy, altered T cell subsets were reported to be associated with increased synthesis of IgA(15–19)). The altered IL-2 production and the expression of IL-2 receptor might be involved in the pathogenesis of IgA nephropathy(20–23)). METHODS: 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, interleukih-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. RESULTS: The mean percentages of T helper/inducer cells (CD(4)), T suppressor/cytotoxic cells (CD(8)) end the CD(4)/CD(8) ratio of the patients were not different from those of controls and the proportions of CD(8) CD(11b) 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 (CD(25)) before the stimulation with PHA in patients were 1.22±1.00 percents and were not different from those in controls (1.12±0.78 percents). The correlations between the production of IL-2 and the concentrations of serum IgA, the degrees of histologic alterations and the proportions of CD(8) and CD(8)CD(11b) 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 CD(4) cells, and the CD(4/)CD(8) 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). CONCLUSIONS: It seemed that patients with IgA nephropathy have an 'latent' cellular immunoregulatory dysfunciton that becomes apparent on the stimulation of extrinsic antigens or mitogens.