A model based upon trafficking of antigen-presenting cells (APCs) to explain the contralateral effect. Introduction of a suitable vector, in this example one encoding viral interleukin-10 (vIL-10), into an inflamed joint transduces synovium and APCs. Lymphocytes are very difficult to transduce, as reflected in the figure. Intra-articular antigen presentation thus occurs in the presence of a high local concentration of vIL-10 produced by the synovium, the APC, or both. Under these conditions, the immune response deviates toward a therapeutic Th2 response. Lymphocytes and APCs then traffic to other joints via the blood stream or lymphatics, where they suppress disease. Reprinted with permission .