B7-1 and B7-2 co-stimulatory molecules are required for mercury-induced autoimmunity.
B7-1 (CD80) and B7-2 (CD86) molecules on antigen presenting cells play important roles in providing co-stimulatory signals required for activation and expansion of autoreactive T cells. Moreover, some reports have suggested that these molecules may have distinct functions in the differentiation of Th1 and Th2 cells. Mercury-induced autoimmunity in H-2s mice is characterized by lymphoproliferation of T and B cells, serum increases in IgG1 and IgE and production of antinucleolar antibodies (ANoA). The mechanisms responsible for the various manifestations of this syndrome have yet to be elucidated. To examine the contributions of B7 co-stimulatory molecules to this model, susceptible mice were treated with antibodies to B7-1, B7-2, or both during the development of mercury-induced autoimmunity. The combination of anti-B7-1 and anti-B7-2 antibodies prevented Hg-induced disease in H-2s mice. Additionally, single anti-B7-1 antibody treatment was sufficient to prevent Hg-induced ANoA production, but not IgG1 and IgE hypergammaglobulinaemia. Further, single antibody treatment with anti-B7-2 resulted in a partial reduction of ANoA titres but had no significant effect on total serum IgG1 and IgE levels. Taken together, these results indicate that B7-1 and B7-2 molecules are critical for the development of Hg-induced autoimmunity and suggest that the different manifestations of the syndrome are regulated by independent mechanisms.
Bagenstose
L M
LM
Department of Microbiology and Immunology, Temple University School of Medicine, PA 19104, USA.
Class
R
R
Salgame
P
P
Monestier
M
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D008628:Mercury / Q000633:toxicity*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000974:Antibodies, Antinuclear; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D008628:Mercury