Volume 3 Supplement 1

Innovative Rheumatology: Gene and Cell Therapies of Arthritis and Related Autoimmune Disorders. Second International Meeting

Open Access

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

  • A Nakajima1, 2, 3,
  • CM Seroogy1,
  • MR Sandora1,
  • IH Tarner,
  • GL Costa1,
  • C Taylor-Edwards1,
  • MH Bachman2,
  • CH Contag and
  • C Garrison-Fathman1
Arthritis Research & Therapy20013(Suppl 1):P37

https://doi.org/10.1186/ar364

Received: 6 April 2001

Published: 25 April 2001

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.

Authors’ Affiliations

(1)
Department of Medicine, Division of Immunology and Rheumatology
(2)
Department of Pediatrics, Stanford University, School of Medicine
(3)
Department of Joint disease and Rheumatism, Nippon Medical School

Copyright

© BioMed Central Ltd 2001

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