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 be 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 agents. To examine the ability and efficiency of such T cells as a vehicle, we employed an experimentally induced model of arthritis. Splenic T cells from DO11.10 TCR transgenic mice specific for OVA were transduced with murine IL-10. Adoptive transfer of the IL-10-transduced DO11.10 splenocytes ameliorated OVA-induced arthritis despite the presence of around 95% nontransduced cells. Using green fluorescent protein as a marker for selection, the number of transferred cells needed to ameliorate the disease was able to be reduced to 10(4). Preferential accumulation of the transferred T cells was observed in the inflamed joint, and the improvement in the disease was not accompanied by impairment of the systemic immune response to the Ag, suggesting that the transferred T cells exert their anti-inflammatory task locally, mainly 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 autoantigen is still unknown.
Setoguchi
K
K
Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Misaki
Y
Y
Araki
Y
Y
Fujio
K
K
Kawahata
K
K
Kitamura
T
T
Yamamoto
K
K
D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000235:genetics*; D005260:Female; D005822:Genetic Vectors / Q000276:immunology / Q000378:metabolism; D049452:Green Fluorescent Proteins; D007111:Immunity, Cellular / Q000235:genetics; D007270:Injections, Intra-Articular; D016753:Interleukin-10 / Q000235:genetics*; D007596:Joints / Q000276:immunology / Q000473:pathology; D008164:Luminescent Proteins / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D012190:Retroviridae / Q000235:genetics / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000276:immunology; D012720:Severity of Illness Index; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D014161:Transduction, Genetic
D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D008164:Luminescent Proteins; C029180:methylated bovine serum albumin; D016753:Interleukin-10; D049452:Green Fluorescent Proteins; D012710:Serum Albumin, Bovine; D010047:Ovalbumin