Long-term effects of IFN-gamma, IL-10, and TGF-beta-modulated dendritic cells on immune response in Lewis rats

Increasing data have shown that IFN-gamma, IL-10, and TGF-beta-modulated dendritic cells (DC) provide a promising strategy in treatment of experimental allergic encephalomyelitis and experimental autoimmune myasthenia gravis through different manner. To explore the immune response status after long-term application of these cytokine-modulated-DC, Lewis rats were injected subcutaneously into naive DC and IFN-gamma, IL-10, and TGF-beta-modulated DC (i.e., IFN-gamma-DC, IL-10-DC, and TGF-beta-DC) at does of 1 x 10(6) cells/rat every month for continuous 18 months, respectively. No rats suffered from decreased vigor and activity as well as cachectic condition during 18-month observation, and no rats had body-weight loss after 18-month treatment. Exploratory laparectomy did not find any tumor in all rats. IL-10-DC and TGF-beta-DC resulted in lower nonspecific (Con A-induced) and antigen specific (ovalbumin-stimulated) spleen mononuclear cells proliferation, accompanied by lower levels of IFN-gamma, IL-10, and TNF-alpha. On the contrary, IFN-gamma-DC did not suppress cell proliferation and IFN-gamma and IL-10 production except only slightly decreased TNF-alpha levels. These results suggest that IFN-gamma-DC seems to be a more ideal candidate in the treatment of autoimmune diseases without suppressing immune response.