INTERACTIONS OF METALLOTHIONEIN WITH MURINE LYMPHOCYTES - PLASMA-MEMBRANE BINDING AND PROLIFERATION

Metallothionein (MT) is a thiol rich protein that has been well charac terized for its ability to bind and sequester heavy metal cations, fre e radicals and other reactive toxicants. In addition to induction by t hese 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 prol iferation 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 proce ssed antigen. In this report, we describe the effects of MT on specifi c lymphocyte subpopulations in order to further characterize the mecha nism of MT-mediated alterations of immune activity. MT binds to the pl asma membrane of both T and B lymphocytes, but, in the absence of a co stimulatory agent, MT induces lymphoproliferation only in B cells. MT also enhances the capacity of naive B lymphocytes to differentiate int o plasma cells. These results demonstrate differential immunomodulator y activities of MT and may explain some of the diverse immunoregulator y effects associated with exposure to environmental toxins.