ICOS-B7 homologous protein interactions are necessary for mercury-induced autoimmunity.
After exposure to subtoxic doses of heavy metals such as mercury, H-2(s) mice develop an autoimmune syndrome consisting of the rapid production of IgG autoantibodies that are highly specific for nucleolar autoantigens and a polyclonal increase in serum IgG1 and IgE. In this study, we explore the role of one of the members of the CD28-B7 costimulation families, ICOS-B7 homologous protein (B7h), in the regulation of mercury-induced autoimmunity. The expression of ICOS on T cells was more enhanced in susceptible A.SW mice than in non-responsive C57BL/6 and DBA/2 mice after HgCl(2) treatment. Furthermore, in A.SW mice treated with HgCl(2), administration of a blocking anti-ICOS Ab effectively inhibited anti-nucleolar autoantibodies and total serum IgE production. Taken together, these results indicate that the ICOS-B7h costimulation pathway is required for this autoimmune syndrome and suggest that targeting this pathway might have therapeutic benefits for human autoimmune diseases.
Zheng
Yan
Y
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Jost
Monika
M
Gaughan
John P
JP
Class
Reiner
R
Coyle
Anthony J
AJ
Monestier
Marc
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015703:Antigens, CD / Q000378:metabolism* / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000235:genetics / Q000517:prevention & control; D018122:B7-1 Antigen / Q000378:metabolism* / Q000502:physiology; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D007108:Immune Tolerance / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D060889:Inducible T-Cell Co-Stimulator Protein; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D008627:Mercuric Chloride / Q000633:toxicity*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA
D000974:Antibodies, Antinuclear; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; C556692:ICOS protein, human; C556694:Icos protein, mouse; D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein; D008562:Membrane Glycoproteins; D007073:Immunoglobulin E; D008627:Mercuric Chloride