The in vitro proliferation of murine lymphocytes to mercuric chloride is restricted to mature T cells and is interleukin 1 dependent

Abstract

The aims of this study were to compare the in vitro responses of murine lymphocytes to HgCl 2 to determine the requirement for adherent cells, and the contribution that costimulation plays in T cell proliferation. The in vitro proliferative response of murine splenocytes to HgCl 2 was found to be both cell concentration- and HgCl 2 concentration-dependent with the greatest response occurring with 5×10 6 cells/ml in the presence of 10 −5 M HgCl 2. Both CD4 + and CD8 + T cells proliferated in response to HgCl 2, but B cells and immature T cells (thymocytes) did not. Proliferation required the presence of splenic adherent cells and was inhibited by addition of anti-IL-1α antibodies. Antibodies to the other co-stimulatory molecules CD40 ligand, CD80 (B7-1), and CD86 (B7-2), although inhibitory, were less effective. Xenobiotics such as the heavy metal mercury can elicit a spectrum of immunological responses ranging from imuunosuppression to autoimmunity. The most common response, in vivo and in vitro, is lymphoproliferation, which may be a prelude to immune activation. Although a number of the requirements for mercury-induced T cell proliferation in vitro have been described, the role that adherent cells play remains to be explained. The studies described here show that interaction between co-stimulatory molecules of adherent cells and mature T cells contributes to HgCl 2-induced T cell proliferation. Among these co-stimulatory molecules, IL-1 appears to play an important role. The requirement for mature T cells, adherent cells, and co-stimulatory molecules argues that HgCl 2-induced T cell proliferation possesses the properties of an antigen-induced response.