In vitro effects of HgCl2 on murine lymphocytes. II. Selective activation of T cells expressing certain V beta TCR.
In vivo administration of HgCl2 causes autoimmune manifestations in susceptible rats and mice. We have previously shown that mercury is a unique molecule that can primarily activate murine T lymphocytes to transformation and proliferation in vitro. To test whether a specific TCR repertoire predisposes the autoimmune development induced by HgCl2 and our hypothesis that mercury may function as a superantigen, we examined the TCR V beta repertoire in HgCl2-stimulated T cells from the responder BALB/c or SJL mice and the non-responder DBA/2 mice. We found a selective activation of T cells bearing a certain set of TCR B beta chains in response to HgCl2, e.g. V beta 6, V beta 8, V beta 10 and V beta 14 in the BALB/c strain. Moreover, depletion of V beta 8+ T cells, a family predominantly expanded in the BALB/c strain upon HgCl2 stimulation, profoundly inhibited the response to HgCl2 in this strain. An alternative selection of V beta segments, involving V beta 6, V beta 7 and V beta 14, was observed in the SJL strain in which the V beta 8 family is genetically deleted. Mechanism(s) whereby mercury modulates the immune system under a stringent genetic control and a possible therapeutic regime against mercury-induced autoimmune disease by administration of antibody specific to the TCR V beta region are discussed.
Jiang
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Y
Department of Immunology, Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Möller
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G
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects*; D008627:Mercuric Chloride / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis*; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D008627:Mercuric Chloride