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      Retrovirally-engineered antigen-specific T cells home to the inflamed joints and suppress collagen-induced arthrtis

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      1 , 2 , 3 , 1 , 1 , , 1 , 1 , 2 , , 1
      Arthritis Research
      BioMed Central
      Innovative Rheumatology: Gene and Cell Therapies of Arthritis and Related Autoimmune Disorders. Second International Meeting
      17-18 May 2001

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          Abstract

          Objective Autoantigen-specific T cells have tissue-specific homing properties, suggesting that these cells may be ideal vehicles for the local delivery of 'immunoregulatory molecules'. We tested this hypothesis by using type II collagen (CII)-specific CD4' Thybridomas, or prim CD4' T cells following gene transfer as vehicles to deliver 'immune regulatory protein' for treatment of collagen-induced arthritis (CIA). Method CII-specific T cells were transduced to express IL-12 antagonist IL-12 p4O, using retroviral vectors, and were transferred into CIA mice. To directly examine whether CII-specific T cells home to the site of inflammation, we transduced a GFP-luciferase fusion protein gene into CII-specific T cells and tested the patterns of cell trafficking using whole-body bioluminescence. Results Transfer of CII-specific IL12 p4O producing CD4'+T cells after primary immunization significantly inhibited the development of CIA. The beneficial effect of IL-12 p4O-transduced T cells for CIA requires TCR spcificity against CII. Using bioluminescence, we found that CII-reactive T cell hybridomas accumulated and remained in inflamed joints when transferred into CII-immunized arthritic mice. Conclusion These results indicated at the local delivery of IL12p4O by T cells inhibited CIA by suppressing an autoimmune response at the site of inflammation. We conclude that modifying antigen-specific T cells by retroviral transduction for local expression of regulatory proteins is a promising therapeutic strategy for the treatment of RA.

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          Author and article information

          Conference
          Arthritis Res
          Arthritis Research
          BioMed Central
          1465-9905
          1465-9913
          2001
          25 April 2001
          : 3
          : Suppl 1
          : P37
          Affiliations
          [1 ]Department of Medicine, Division of Immunology and Rheumatology
          [2 ]Department of Pediatrics, Stanford University, School of Medicine, Stanford, CA, USA
          [3 ]Department of Joint disease and Rheumatism, Nippon Medical School, Tokyo, Japan
          Article
          ar364
          10.1186/ar364
          3272725
          a5cea4e5-1c5a-45bb-8f8c-b1e03f85a10c
          Copyright ©2001 BioMed Central Ltd
          Innovative Rheumatology: Gene and Cell Therapies of Arthritis and Related Autoimmune Disorders. Second International Meeting
          Montpellier, France
          17-18 May 2001
          History
          : 6 April 2001
          Categories
          Meeting Abstract

          Orthopedics
          Orthopedics

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