RRC ID 12160
Author Setoguchi K, Misaki Y, Araki Y, Fujio K, Kawahata K, Kitamura T, Yamamoto K.
Title Antigen-specific T cells transduced with IL-10 ameliorate experimentally induced arthritis without impairing the systemic immune response to the antigen.
Journal J Immunol
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.
Volume 165(10)
Pages 5980-6
Published 2000-11-15
DOI 10.4049/jimmunol.165.10.5980
PMID 11067961
MeSH Animals Antigens / administration & dosage Antigens / immunology* Antigens / pharmacology Arthritis, Experimental / genetics Arthritis, Experimental / immunology* Arthritis, Experimental / pathology Arthritis, Experimental / therapy* CD4-Positive T-Lymphocytes / immunology CD4-Positive T-Lymphocytes / metabolism CD4-Positive T-Lymphocytes / transplantation* Cell Movement / genetics Cell Movement / immunology Dose-Response Relationship, Immunologic Epitopes, T-Lymphocyte / genetics* Female Genetic Vectors / immunology Genetic Vectors / metabolism Green Fluorescent Proteins Immunity, Cellular / genetics Injections, Intra-Articular Interleukin-10 / genetics* Joints / immunology Joints / pathology Luminescent Proteins / biosynthesis Lymphocyte Activation / genetics Lymphocyte Count Lymphocyte Transfusion Mice Mice, Inbred BALB C Mice, Transgenic Ovalbumin / administration & dosage Ovalbumin / immunology* Ovalbumin / pharmacology Retroviridae / genetics Retroviridae / immunology Serum Albumin, Bovine / immunology Severity of Illness Index Spleen / cytology Spleen / immunology Spleen / metabolism Spleen / transplantation Transduction, Genetic*
IF 4.886
Times Cited 35
DNA material pMFGmIL10 (RDB1446)