Antigen-specific T cells transduced with IL-10 ameliorate experimentally induced arthritis without impairing the systemic immune response to the antigen

For the treatment of rheumatoid arthritis, efficient drug delivery methods to the inflamed joints need to he developed. Because T cells expressing an appropriate autoantigen-specific receptor can migrate to inflamed lesions, it has been reasoned that they can be employed to deliver therapeutic agent s. To examine the ability and efficiency of such T cells as a vehicle, we e mployed an experimentally induced model of arthritis. Splenic T cells from DO11,10 TCR transgenic mice specific for OVA were transduced with murine IL -IO, Adoptive transfer of the IL-10-transduced DO11,10 splenocytes ameliora ted OVA-induced arthritis despite the presence of around 95% nontransduced cells. Using green fluorescent protein as a marker for selection, the numbe r of transferred cells needed to ameliorate the disease was able to be redu ced to 10(4). Preferential accumulation of the transferred T cells was obse rved in the inflamed joint, and the improvement in the disease was not acco mpanied by impairment of the systemic Immune response to the Ag, suggesting that the transferred T cells exert their anti-inflammatory task locally, m ainly in the joints where the Ag exists. In addition, IL-10-transduced DO11 ,10 T cells ameliorated methylated BSA-induced arthritis when the arthritic joint was coinjected with OVA in addition to methylated BSA, These results suggest that T cells specific for a joint-specific Ag would be useful as a therapeutic vehicle in rheumatoid arthritis for which the arthritic autoan tigen is still unknown.