Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK.
Toxicol Sci. 2013 Jul;134(1):49-63. doi: 10.1093/toxsci/kft099. Epub 2013 May 2.
Noninvasive vaginal infections by Staphylococcus aureus strains producing the superantigen TSST-1 can cause menstrual toxic shock syndrome (mTSS). With the objective of exploring the basis for differential susceptibility to mTSS, the relative responsiveness to TSST-1 of healthy women has been investigated. Peripheral blood mononuclear cells from healthy donors were incubated with purified TSST-1 or with the T-cell mitogen phytohemmaglutinin (PHA), and proliferation was measured. The concentrations of TSST-1 and PHA required to elicit a response equivalent to 15% of the maximal achievable response (EC15) were determined. Although with PHA, EC15 values were comparable between donors, subjects could be classified as being of high, medium, or low sensitivity based on responsiveness to TSST-1. Sensitivity to TSST-1-induced proliferation was associated with increased production of the cytokines interleukin-2 and interferon-γ. When the entire T lymphocyte population was considered, there were no differences between sensitivity groups with respect to the frequency of cells known to be responsive to TSST-1 (those bearing CD3(+) Vβ2(+)). However, there was an association between sensitivity to TSST-1 and certain HLA-class II haplotypes. Thus, the frequencies of DR7DQ2, DR14DQ5, DR4DQ8, and DR8DQ4 haplotypes were greater among those with high sensitivity, a finding confirmed by analysis of responses to immortalized homozygous B cell lines. Collectively, the results reveal that factors other than neutralizing antibody and the frequency of Vβ2(+) T lymphocytes determine immunological responsiveness to TSST-1. Differential responsiveness of lymphocytes to TSST-1 may form the basis of interindividual variations in susceptibility to mTSS.
金黄色葡萄球菌产生超抗原 TSST-1 的非侵入性阴道感染可导致月经中毒性休克综合征（mTSS）。为了探讨对 mTSS 易感性差异的基础，研究了健康女性对 TSST-1 的相对反应性。用纯化的 TSST-1 或 T 细胞有丝分裂原植物血球凝集素（PHA）孵育健康供体的外周血单核细胞，并测量增殖。确定产生相当于最大可实现反应的 15%的反应（EC15）所需的 TSST-1 和 PHA 的浓度。尽管用 PHA，EC15 值在供体之间具有可比性，但可以根据对 TSST-1 的反应性将受试者分类为高、中或低敏感性。对 TSST-1 诱导的增殖的敏感性与细胞因子白细胞介素-2 和干扰素-γ的产生增加有关。当考虑整个 T 淋巴细胞群体时，在对 TSST-1 有反应的细胞（那些携带 CD3(+) Vβ2(+)）的频率方面，敏感组之间没有差异。然而，对 TSST-1 的敏感性与某些 HLA 类 II 单倍型有关。因此，在对 TSST-1 具有高敏感性的个体中，DR7DQ2、DR14DQ5、DR4DQ8 和 DR8DQ4 单倍型的频率更高，这一发现通过对永生同源 B 细胞系的反应分析得到了证实。总之，结果表明，决定对 TSST-1 免疫反应性的因素不仅包括中和抗体和 Vβ2(+)T 淋巴细胞的频率。淋巴细胞对 TSST-1 的不同反应性可能是个体对 mTSS 易感性差异的基础。
