title: Antigen-specific T cells transduced with IL-10 ameliorate experimentally induced arthritis without impairing the systemic immune response to the antigen.
abstract: 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.
authors.affiliation: Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Setoguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Misaki
authors.forename: Y
authors.initials: Y
authors.lastname: Araki
authors.forename: K
authors.initials: K
authors.lastname: Fujio
authors.forename: K
authors.initials: K
authors.lastname: Kawahata
authors.forename: T
authors.initials: T
authors.lastname: Kitamura
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: 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
chemical_list: 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