Jiang Y, Möller G
Department of Immunology, Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Int Immunol. 1996 Nov;8(11):1729-36. doi: 10.1093/intimm/8.11.1729.
In vivo administration of HgCl2 causes autoimmune manifestations in susceptible rats and mice. We have previously shown that mercury is a unique molecule that can primarily activate murine T lymphocytes to transformation and proliferation in vitro. To test whether a specific TCR repertoire predisposes the autoimmune development induced by HgCl2 and our hypothesis that mercury may function as a superantigen, we examined the TCR V beta repertoire in HgCl2-stimulated T cells from the responder BALB/c or SJL mice and the non-responder DBA/2 mice. We found a selective activation of T cells bearing a certain set of TCR B beta chains in response to HgCl2, e.g. V beta 6, V beta 8, V beta 10 and V beta 14 in the BALB/c strain. Moreover, depletion of V beta 8+ T cells, a family predominantly expanded in the BALB/c strain upon HgCl2 stimulation, profoundly inhibited the response to HgCl2 in this strain. An alternative selection of V beta segments, involving V beta 6, V beta 7 and V beta 14, was observed in the SJL strain in which the V beta 8 family is genetically deleted. Mechanism(s) whereby mercury modulates the immune system under a stringent genetic control and a possible therapeutic regime against mercury-induced autoimmune disease by administration of antibody specific to the TCR V beta region are discussed.
在体内给予氯化汞会在易感大鼠和小鼠中引发自身免疫表现。我们之前已经表明，汞是一种独特的分子，它能够在体外主要激活鼠T淋巴细胞发生转化和增殖。为了测试特定的T细胞受体（TCR）库是否使机体易患由氯化汞诱导的自身免疫性疾病，以及我们关于汞可能作为超抗原发挥作用的假设，我们检测了来自有反应的BALB/c或SJL小鼠以及无反应的DBA/2小鼠的经氯化汞刺激的T细胞中的TCR Vβ库。我们发现，在对氯化汞的反应中，携带某一组TCR Bβ链的T细胞被选择性激活，例如在BALB/c品系中Vβ6、Vβ8、Vβ10和Vβ14。此外，Vβ8⁺T细胞耗竭（这是一个在BALB/c品系中经氯化汞刺激后大量扩增的家族），显著抑制了该品系对氯化汞的反应。在Vβ8家族基因缺失的SJL品系中，观察到了涉及Vβ6、Vβ7和Vβ14的Vβ片段的另一种选择。本文讨论了汞在严格的基因控制下调节免疫系统的机制，以及通过给予针对TCR Vβ区域的特异性抗体来治疗汞诱导的自身免疫性疾病的可能方案。
