| 15728528 |
Zheng Y, Jost M, Gaughan JP, Class R, Coyle AJ, Monestier M: ICOS-B7 homologous protein interactions are necessary for mercury-induced autoimmunity. J Immunol. 2005 Mar 1;174(5):3117-21.
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. |
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