Interactions of metallothionein with murine lymphocytes: Plasma membrane binding and proliferation

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.