Ohara-Nemoto Y, Kaneko M
Department of Microbiology, School of Dentistry, Iwate Medical University, Morioka, Japan.
Can J Microbiol. 1996 Nov;42(11):1104-11. doi: 10.1139/m96-142.
Streptococcal pyrogenic exotoxin type C (SPE C) is a member of the bacterial superantigens that are potent stimulants of T cells. We expressed SPE C in Escherichia coli and characterized its selective stimulation properties on human T cells bearing specific V beta chains of T-cell receptors (TCRs). Cytokine profiles induced by SPE C were also examined. Recombinant SPE C significantly enhanced proliferation of human peripheral blood mononuclear cells (PBMCs) at concentrations as low as 10(-12)-10(-14)M. Reverse transcription of RNA, from SPE-C-stimulated PBMCs followed by polymerase chain reaction, revealed selective induction of TCR V beta 2 chain expression. SPE C raised the mRNA level of type 1 helper T cell (TH1) related cytokines, such as interferon gamma (IFN-gamma), interleukin 2 (IL-2), and tumor necrosis factor beta (TNF beta). The expression of TNF alpha was also increased. In contrast, the increase in mRNA levels of the p35 small fragment of IL-12 and type 2 helper T cell (TH2) related cytokines (i.e., IL-4 and IL-10) was not significantly affected by SPE C. The mRNA level of proinflammatory cytokine IL-6 was increased marginally. Consistent with the mRNA accumulation, protein concentrations of IFN gamma, IL-2, and TNF were increased in SPE-C-stimulated PBMCs, but IL-4 was not. From these results, we conclude that the stimuli of SPE C preferentially causes the TH1 responses in human T cells bearing TCR V beta 2.
C 型链球菌致热外毒素(SPE C)是细菌超抗原家族的成员,是 T 细胞的强效刺激物。我们在大肠杆菌中表达了 SPE C,并对其对携带特定 T 细胞受体(TCR)Vβ链的人 T 细胞的选择性刺激特性进行了表征。还检测了 SPE C 诱导的细胞因子谱。重组 SPE C 在低至 10^(-12)-10^(-14)M 的浓度下就能显著增强人外周血单个核细胞(PBMC)的增殖。对经 SPE-C 刺激的 PBMC 进行 RNA 逆转录,随后进行聚合酶链反应,结果显示 TCR Vβ2 链表达被选择性诱导。SPE C 提高了 1 型辅助性 T 细胞(TH1)相关细胞因子的 mRNA 水平,如干扰素γ(IFN-γ)、白细胞介素 2(IL-2)和肿瘤坏死因子β(TNFβ)。TNFα的表达也有所增加。相比之下,IL-12 的 p35 小片段和 2 型辅助性 T 细胞(TH2)相关细胞因子(即 IL-4 和 IL-10)的 mRNA 水平升高并未受到 SPE C 的显著影响。促炎细胞因子 IL-6 的 mRNA 水平略有升高。与 mRNA 积累情况一致,在经 SPE-C 刺激的 PBMC 中,IFNγ、IL-2 和 TNF 的蛋白浓度升高,但 IL-4 未升高。从这些结果中,我们得出结论,SPE C 的刺激优先在携带 TCR Vβ2 的人 T 细胞中引发 TH1 反应。