Abdelnour A, Tarkowski A
Department of Clinical Immunology, University of Göteborg, Sweden.
Cell Immunol. 1993 Apr 1;147(2):279-93. doi: 10.1006/cimm.1993.1069.
We have recently described a murine model of Staphylococcus aureus-induced septic arthritis. One of the hallmarks of this disease is a striking hypergammaglobulinemia. In the present study we have used a sensitive ELISPOT technique to assess, at the single cell level, the B-cell differentiation properties of this arthritogenic, toxic shock syndrome toxin-1 (TSST-1)-producing staphylococcal strain. In vivo, inoculation of live S. aureus resulted in lymphoproliferation, early (within 3-4 days) peak of IgM-secreting cells and late (2 weeks after the injection) pronounced increase of IgG-secreting cells. We have documented that this late increase of IgG-secreting cells is a CD4+ T-cell-dependent phenomenon. Furthermore, we have showed that there is a relationship between the hypergammaglobulinemia and the appearance of arthritis, since a nonarthritogenic staphylococcal strain will not give rise to increased frequency of immunoglobulin-secreting cells. To elucidate mechanisms responsible for S. aureus-induced polyclonal B-cell activation, we have assessed in vitro effects of formalin-fixed arthritogenic S. aureus on the release of cytokines. Our results show that the S. aureus LS-1 strain induces in vitro preferentially IgM-secreting cells, many of them displaying autoantibody properties. The magnitude of this response is high and comparable with optimal concentrations of LPS, a potent murine polyclonal B-cell activator. Interleukin-1 alpha (IL-1 alpha), tumor necrosis factor (TNF), and interleukin-6 (IL-6) were all secreted by mouse MNC after in vitro exposure to formalin-killed S. aureus. Inhibition experiments, using neutralizing antibodies to these cytokines, revealed that IL-1 alpha and IL-6 but not TNF-alpha had potent B-cell differentiation properties in S. aureus-stimulated cell cultures.
我们最近描述了一种金黄色葡萄球菌诱导的脓毒性关节炎小鼠模型。这种疾病的一个特征是显著的高球蛋白血症。在本研究中，我们使用了一种灵敏的酶联免疫斑点技术，在单细胞水平评估这种产生致关节炎性中毒性休克综合征毒素-1（TSST-1）的葡萄球菌菌株的B细胞分化特性。在体内，接种活的金黄色葡萄球菌导致淋巴细胞增殖，早期（3-4天内）IgM分泌细胞达到峰值，晚期（注射后2周）IgG分泌细胞显著增加。我们已经证明，这种IgG分泌细胞的晚期增加是一种CD4 + T细胞依赖性现象。此外，我们已经表明高球蛋白血症与关节炎的出现之间存在关联，因为非致关节炎性葡萄球菌菌株不会导致免疫球蛋白分泌细胞频率增加。为了阐明金黄色葡萄球菌诱导多克隆B细胞活化的机制，我们评估了福尔马林固定的致关节炎性金黄色葡萄球菌对细胞因子释放的体外影响。我们的结果表明，金黄色葡萄球菌LS-1菌株在体外优先诱导IgM分泌细胞，其中许多具有自身抗体特性。这种反应的强度很高，与强效小鼠多克隆B细胞激活剂LPS的最佳浓度相当。小鼠单核细胞在体外暴露于福尔马林灭活的金黄色葡萄球菌后，均可分泌白细胞介素-1α（IL-1α）、肿瘤坏死因子（TNF）和白细胞介素-6（IL-6）。使用针对这些细胞因子的中和抗体进行的抑制实验表明，在金黄色葡萄球菌刺激的细胞培养物中，IL-1α和IL-6而非TNF-α具有强大的B细胞分化特性。
