title: Effects of the murine genotype on T cell activation and cytokine production in murine mercury-induced autoimmunity.
abstract: Mercury induces a systemic autoimmune condition characterized by auto-antibodies to the nucleolar protein fibrillarin (AFA) and systemic immune-complex (IC) deposits in genetically susceptible mouse strains. This study examines T cell activation and cytokine production following mercury exposure in genetically susceptible and resistant strains. Mercury injected s.c., according to the protocol for induction of autoimmunity, caused an early T cell activation, measured as an increase of IL-2-producing cells, and increased expression of the IL-2-receptor proteins CD25 and CD122 and of the proliferation marker CD71 on days 2-4 in the susceptible A.SW and A. TH strains. This was followed by a long-lasting increase in the number of T cells, dominated by CD4(+) cells. Mice of the susceptible A.SW strain showed a modest increase of TNF-alpha-, IFN-gamma-, and IL-4-producing cells after 4-6 days, and a very distinct increase of IL-4-producing cells on days 8-10. The susceptible SJL strain (H-2(s)), severely deficient in Th2-promoting CD4(+), NK1.1(+) T cells, showed no increase of IL-4(+) cells on days 8-10. Instead, the number of IFN-gamma-producing cells was increased. Susceptible mice developed an increase of Ig-producing cells, AFA, and systemic IC-deposits. Genetically mercury-resistant A.TL mice showed a minimal increase of T cells, but no increase in cytokine-producing cells. We conclude that autoimmunogenic doses of HgCl2 induce an activation and proliferation of T cells in genetically susceptible mouse strains, as well as a broad increase of cytokine-producing cells, followed by a late predominance of the Th2-associated IL-4. One strain, severely deficient in Th2-promoting CD4(+), NK1.1(+) T cells, lacked the increase in IL-4(+) cells, indicating that a predominantly Th2-response is not necessary for induction of autoimmunity by mercury. However, a Th2-dominated response led to a faster and stronger B cell activation.
authors.affiliation: Departments of Pathology, Linköping University, Linköping, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Johansson
authors.forename: B
authors.initials: B
authors.lastname: Sander
authors.forename: P
authors.initials: P
authors.lastname: Hultman
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis*; D005838:Genotype; D015847:Interleukin-4 / Q000096:biosynthesis; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D015847:Interleukin-4; D037181:Lectins, C-Type; D008627:Mercuric Chloride; D000099192:CD69 Antigens