Gold is a T cell polyclonal activator in BN and LEW rats but favors IL-4 expression only in autoimmune prone BN rats

Gold salts are beneficial in the treatment of rheumatoid arthritis but may induce immune-mediated disorders in predisposed patients. Gold salts induce Th2-dependent autoimmunity in Brown-Norway (BN) rats but not in Lewis (LEW ) rats. The aim of this study was to define molecular targets of gold salts and to approach why LEW rats are resistant. Gold salts act on early steps of transduction in T cells from BN and LEW rats since they trigger tyrosine phosphorylation of numerous proteins including p56(Ick) and a calcium sign al which results in IL-4 and IFN-gamma expression by BN and LEW T cells. Ho wever, the IL-4 response was favored in BIN spleen cells in vitro and in vi vo. IFN-gamma, produced in part by CD8(+) cells, contributes to the resista nce of LEW rats since gold salt-injected LEW rats receiving anti-CD8 or ant i-IFN-gamma mAb displayed the parameters characteristics of gold salt-induc ed Th2 autoimmunity although to a lesser extent than in BN rats. Gold salts transduce a signal in BN and LEW spleen cells resulting in IL-4 and IFN-ga mma gene transcription with a preferential IL-4 response in BN rats, a Th2- prone strain, while IFN-gamma contributes to the resistance of LEW rats.