Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced arthritis

Dendritic cells (DCs) are specialized antigen-presenting cells that migrate from the periphery to lymphoid tissues, where they activate and regulate T cells. Genetic modification of DCs to express immunoregulatory molecules w ould provide a new immunotherapeutic strategy for autoimmune and other dise ases. We have engineered bone marrow-derived DCs that express IL-4 and test ed the ability of these cells to control murine collagen-induced arthritis (CIA), a model for rheumatoid arthritis in which Th1 cells play a critical role. IL-4-transduced DCs inhibited Th1 responses to collagen type II in vi tro. A single injection of IL-4-transduced DCs reduced the incidence and se verity of CIA and suppressed established Th1 responses and associated humor al responses, despite only transient persistence of injected DCs in the spl een. In contrast, control DCs and IL-4-transduced T cells or fibroblastic c ells failed to alter the course of the disease. The functional effects corr elated well with the differential efficiency of DC migration from various s ites of injection to lymphoid organs, especially the spleen. The ability of splenic T cells to produce IL-4 in response to anti-CD3 was enhanced after the administration of IL-4-transduced DCs. These results support the feasi bility of using genetically modified DCs for the treatment of autoimmune di sease.