Studies on the pathogenesis of glomerulonephritis and vascultitis induced by superantigen.

背景。我们之前报道了10例与耐甲氧西林金黄色葡萄球菌（MRSA）感染相关的肾小球肾炎（GN）患者，其DR+CD4+和DR+CD8+亚群中的T细胞以及表达几种T细胞受体（TCR） Vb+细胞的T细胞显著增加，这可能代表MRSA衍生的超抗原激活了Vb特异性T细胞（Kidney Int 1995; 47: 207-2 16）。此外，为了更好地了解细菌超抗原和细胞因子在MRSA相关gn发病机制中的作用，我们检测了细胞因子、T淋巴细胞亚群、自然杀伤NK细胞、记忆T细胞和IL-2受体的表达水平。对22例MRSA感染后发生葡萄球菌性肠毒素所致肾小球肾炎（GN）的患者进行免疫学评价，并与未发生GN的MRSA感染患者（非GN组）和正常人进行比较。外周淋巴细胞中，GN组表达几种TCR Vb的T细胞频率，特别是vb5家族TCR的频率高于非GN组和正常健康对照。GN患者还显示血清中几种细胞因子水平升高，包括肿瘤坏死因子-a、白细胞介素-1b （IL-1b）、IL-2、IL-6、IL-8和il - 10，这些细胞因子被认为是肾炎发病的原因。GN组记忆细胞和IL-2受体水平明显高于正常人。结论：这些结果提示，被mrsa来源的葡萄球菌肠毒素激活的T细胞和随后产生的细胞因子可能在mrsa相关GN的发病机制中起重要作用。

Background. We have previously reported that 10 patients who developed glomerulonephritis (GN) in association with methicillin-resistant staphylococcus aureus (MRSA) infection showed a marked increase in T cells both in DR+CD4+ and DR+CD8+ subsets and in T cells expressing several T cell receptor (TCR) Vb+ cells, perhaps representing Vb-specific T cell activation by MRSA-derived superantigens (Kidney Int 1995 ; 47 : 207-2 16). Moreover, we tested levels of cytokines, T-lymphocy te subsets, natural killer NK cells, memory T cells, and the expression of IL-2 receptors in order to better understand the role of bacterial superantigens and cytokines in the pathogenesis of MRSA- associated GN.Methods. Twenty-two patients with MRSA infection who later developed glomerulonephritis (GN) caused by staphylococcal enterotoxin were evaluated immunologically in comparison with patients whose MRSA infection was not followed by GN (non-GN group) and normal individuals.Results. Among peripheral lymphocytes, frequency of T cells expressing several TCR Vb's, especially Vb5-family TCR was higher in GN group than in the non-GN group as well as in normal healthy control. GN patients also showed increased serum levels of several cytokines, including tumor necrosis factor-a, interleukin-1b (IL-1b), IL-2, IL-6, IL-8, and IL-l0, which have been suggested to be responsible for the onset of nephritis. Memory cells, and IL-2 receptors also were elevated in GN group than in normal individuals.Conclusion, These results suggest that T cells activated by MRSA-derived staphylococcal enterotoxins and subsequent production of cytokines may play important roles in the pathogenesis of MRSA-associated GN.