Borghesi L A, Youn J, Olson E A, Lynes M A
Department of Molecular and Cell Biology, University of Connecticut, Storrs, 06269, USA.
Toxicology. 1996 Apr 15;108(1-2):129-40. doi: 10.1016/s0300-483x(95)03243-9.
Metallothionein (MT) is a thiol rich protein that has been well characterized for its ability to bind and sequester heavy metal cations, free radicals and other reactive toxicants. In addition to induction by these stressors, MT gene expression is upregulated by several cytokines of the acute phase response. In previous work, we have shown that MT can alter aspects of lymphocyte function. MT alone induces modest proliferation of unfractionated splenocytes and acts synergistically with T cell- and B cell-specific mitogens. In contrast, MT inhibits humoral responsiveness in vivo and reduces in vitro T cell responses to processed antigen. In this report, we describe the effects of MT on specific lymphocyte subpopulations in order to further characterize the mechanism of MT-mediated alterations of immune activity. MT binds to the plasma membrane of both T and B lymphocytes, but, in the absence of a costimulatory agent, MT induces lymphoproliferation only in B cells. MT also enhances the capacity of naive B lymphocytes to differentiate into plasma cells. These results demonstrate differential immunomodulatory activities of MT and may explain some of the diverse immunoregulatory effects associated with exposure to environmental toxins.
金属硫蛋白（MT）是一种富含硫醇的蛋白质，因其具有结合和螯合重金属阳离子、自由基及其他反应性毒物的能力而得到充分表征。除了受这些应激源诱导外，MT基因表达还会被急性期反应的几种细胞因子上调。在之前的研究中，我们已经表明MT可以改变淋巴细胞功能的某些方面。单独的MT可诱导未分级脾细胞适度增殖，并与T细胞和B细胞特异性丝裂原协同作用。相比之下，MT在体内抑制体液反应性，并降低体外T细胞对加工抗原的反应。在本报告中，我们描述了MT对特定淋巴细胞亚群的影响，以进一步表征MT介导的免疫活性改变的机制。MT与T淋巴细胞和B淋巴细胞的质膜结合，但在没有共刺激剂的情况下，MT仅在B细胞中诱导淋巴细胞增殖。MT还增强了幼稚B淋巴细胞分化为浆细胞的能力。这些结果证明了MT具有不同的免疫调节活性，并可能解释了与接触环境毒素相关的一些不同的免疫调节作用。
