Rink L, Luhm J, Koester M, Kirchner H
Institute of Immunology and Transfusion Medicine, University of Lübeck, School of Medicine, Germany.
J Interferon Cytokine Res. 1996 Jan;16(1):41-7. doi: 10.1089/jir.1996.16.41.
Superantigens cross-link the MHC class II molecule on accessory cells with the V beta region of the TCR outside the antigen binding sites. In this study, we compared the capacity of the staphylococcal entertoxins (SE) A, B, C1, C2, C3, D, and E, the toxic shock syndrome toxin (TSST) 1, the exfoliative toxin (ExFT) A, and the Streptococcus pyogenes erythrogenic exotoxins (SPE) B and C to induce cytokine release in human peripheral blood mononuclear cells. We showed that all toxins tested induced IL-1 alpha and beta, IL-2, IL-4, IL-6, IFN-gamma, and TNF-alpha, but not IFN-alpha. However, we found that SPEB differed from all other toxins tested, because its cytokine induction was significantly lower than that of the other toxins. This was not true of IL-6 and IL-10 induction, in which SPEB showed similar amounts of IL-6 compared with all other toxins and of IL-10 in comparison to SEC2. SPEB showed a specificity for TH2 cells, whereas the other toxins stimulated TH1 as well as TH2 cells very strongly. As a result, superantigens appear to be able to uncouple the TH1/TH2 antagonism. Collectively, our results indicate that SPEB seems not to be a superantigen or represents a different group of microbial superantigens. Furthermore, superantigens stimulate TH1 as well as TH2 cells without any preference and therefore they are able to induce humoral as well as cellular immunity. This could be one reason for the existence of autoantibodies and autoreactive T cells in autoimmune diseases and one major step in the beginning of the induction of autoreactivity.
超抗原可使辅助细胞上的MHCⅡ类分子与抗原结合位点之外的TCR的Vβ区发生交联。在本研究中，我们比较了葡萄球菌肠毒素（SE）A、B、C1、C2、C3、D和E、中毒性休克综合征毒素（TSST）1、剥脱毒素（ExFT）A以及化脓性链球菌产红疹毒素（SPE）B和C在人外周血单个核细胞中诱导细胞因子释放的能力。我们发现，所有测试毒素均可诱导IL-1α和β、IL-2、IL-4、IL-6、IFN-γ和TNF-α的产生，但不能诱导IFN-α。然而，我们发现SPEB与所有其他测试毒素不同，因为其细胞因子诱导能力显著低于其他毒素。IL-6和IL-10的诱导情况并非如此，其中SPEB与所有其他毒素相比，IL-6的产生量相似，与SEC2相比，IL-10的产生量相似。SPEB对TH2细胞具有特异性作用，而其他毒素对TH1和TH2细胞均有很强的刺激作用。因此，超抗原似乎能够打破TH1/TH2的拮抗作用。总的来说，我们的结果表明，SPEB似乎不是一种超抗原，或者代表了一类不同的微生物超抗原。此外，超抗原对TH1和TH2细胞均无偏好地进行刺激，因此它们能够诱导体液免疫和细胞免疫。这可能是自身免疫性疾病中存在自身抗体和自身反应性T细胞的原因之一，也是自身反应性诱导开始过程中的一个主要步骤。
