The in vitro proliferation of murine lymphocytes to mercuric chloride is restricted to mature T cells and is interleukin 1 dependent.
The aims of this study were to compare the in vitro responses of murine lymphocytes to HgCl2 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 HgCl2 was found to be both cell concentration- and HgCl2 concentration-dependent with the greatest response occurring with 5 x 10(6) cells/ml in the presence of 10(-5) M HgCl2. Both CD4+ and CD8+ T cells proliferated in response to HgCl2, 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-1 alpha 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 immunosuppression 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 HgCl2-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 HgCl2-induced T cell proliferation possesses the properties of an antigen-induced response.
Pollard
K M
KM
W.M. Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. mpollard@scripps.edu
Landberg
G P
GP
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008627:Mercuric Chloride / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*
D000906:Antibodies; D007375:Interleukin-1; D008627:Mercuric Chloride