Staphylococcal superantigens and T cell expansions in Wegener's granulomatosis
Staphylococcal superantigens and T cell expansions in Wegener's granulomatosis
复制标题
DOI：
10.1046/j.1365-2249.2003.02157.x
复制
发表时间：
2003-06-01
影响因子：
4.6
通讯作者：
Tervaert, JWC
中科院分区：
文献类型：
--
作者：
Popa, ER;Stegeman, CA;Tervaert, JWC
韦格纳肉芽肿病(WG)是一种自身免疫性系统性血管炎，慢性携带金黄色葡萄球菌是病情恶化的危险因素。循环T细胞在这种疾病中被持续激活，提示存在慢性刺激。在WG中，慢性携带金黄色葡萄球菌和慢性T细胞激活之间的因果联系是可以想象的，因为金黄色葡萄球菌产生超抗原(SAG)，这是强大的T细胞刺激因子。超抗原刺激导致表达SAG结合的T细胞受体V-β(Vbeta)链的T细胞亚群扩张。在目前的研究中，我们假设在WG中，葡萄球菌SAG的存在伴随着SAG反应的T细胞亚群的扩张。我们在横断面和纵向研究中验证了我们的假设，其中评估了7个葡萄球菌SAG基因[通过聚合酶链式反应(PCR)分型]、8个SAG结合的Vbeta链和4个SAG非结合的Vbeta链(通过流式细胞仪评估)之间的关联。这两项研究都表明，WG患者的T细胞扩增率明显高于健康人，但与金黄色葡萄球菌或其SAG的存在无关。此外，T细胞的扩张通常是小范围的，并且不会同时出现在CD4和CD8亚群中。我们得出结论，在WG中，金黄色葡萄球菌通过超抗原性T细胞激活以外的其他机制影响其假定的致病功能。
In Wegener's granulomatosis (WG), a form of autoimmune systemic vasculitis, chronic carriage of Staphylococcus aureus constitutes a risk factor for the development of exacerbations. Circulating T cells in this disease are persistently activated, suggesting the presence of a chronic stimulus. A causal link between chronic carriage of S. aureus and chronic T cell activation in WG is conceivable, because S. aureus produces superantigens (SAg), which are potent T cell stimulators. Superantigenic stimulation of T cells results in expansion of T cell subsets expressing SAg-binding T cell receptor V-beta (Vbeta) chains. In the present study we hypothesized that in WG the presence of staphylococcal SAg is accompanied by expansion of SAg-reacting T cell subsets. We tested our hypothesis in a cross-sectional and a longitudinal study in which the association between seven staphylococcal SAg genes [typed by poplymerase chain reaction (PCR)], eight SAg-binding Vbeta chains and four SAg-non-binding Vbeta chains (assessed by flow-cytometry) was assessed. Both studies showed that T cell expansions were present at a significantly higher rate in WG patients than in healthy individuals, but were not associated with the presence of either S. aureus or its SAg. Moreover, T cell expansions were generally of small extent, and did not appear simultaneously in both CD4 and CD8 subsets. We conclude that in WG S. aureus effects its supposed pathogenic function by a mechanism other than superantigenic T cell activation.