Suppressed IL-2 production and response in AA rats: role of suppressor cells and the effect of auranofin treatment.

The marked suppression of mitogenic responses to concanavalin A observed in adjuvant arthritic (AA) rats during the development and progression of the clinical disease is mediated primarily by splenic adherent cell population. The suppressed mitogenic response of spleen cells from AA rats was in part due to suppressed production of and response to interleukin 2 (IL-2). Unfractionated spleen cells from AA rats did not produce or respond to IL-2. However, IL-2 production and response were normalized after removal of adherent cells. Reconstitution experiments demonstrated that adherent cells from AA rats suppressed both the mitogenic response and IL-2 production by normal spleen cells. The low IL-2 levels was not a result of degradation or consumption of endogenously produced interleukin. In vitro treatment of suppressor adherent cells from AA rats with micromolar concentrations of auranofin (AF), but not gold sodium thiomalate, totally abolished the suppression of both mitogenesis and IL-2 production. Our studies demonstrate that the suppressed lymphocyte mitogenic responses, IL-2 response and IL-2 production of AA rat spleen cells are due to the presence of suppressor adherent cells, and that treatment with AF inhibited suppressor cell activity and restored to normal levels lymphocyte mitogenic responses and IL-2 production.