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

Nihon Rinsho Meneki Gakkai Kaishi. 2000 Dec;23(6):538-41. doi: 10.2177/jsci.23.538.
[Article in Japanese]

Abstract

For the treatment of rheumatoid arthritis, efficient drug delivery methods to the inflamed joints need to be developed. Since 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. In order 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 DO 11.10 T cell receptor transgenic mice specific for OVA were transduced with murine IL-10. Adoptive transfer of the IL-10-transduced DO 11.10 splenocytes ameliorated OVA-induced arthritis, in spite of the presence of around 95% non-transduced cells. Using GFP 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 antigen, suggesting that the transferred T cells exert their antiinflammatory task locally, mainly in the joints where the antigen exists. In addition, IL-10-transduced DO 11.10 T cells ameriolated mBSA-induced arthritis when the arthritic joint was co-injected with OVA in addition to mBSA. These results suggest that T cells specific for a joint specific antigen would be useful as a therapeutic vehicle in rheumatoid arthritis for which the arthritic autoantigen is still unknown.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / therapy*
  • Disease Models, Animal
  • Genetic Therapy / methods*
  • Interleukin-10 / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / immunology*
  • Transduction, Genetic

Substances

  • Receptors, Antigen, T-Cell
  • Interleukin-10