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

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).

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.

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.

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.

Affiliations

1. Department of Medicine, Division of Immunology and Rheumatology, USA

   • A Nakajima
   • , CM Seroogy
   • , MR Sandora
   • , GL Costa
   • , C Taylor-Edwards
   •  & C Garrison-Fathman

2. Department of Pediatrics, Stanford University, School of Medicine, Stanford, CA, USA

   • A Nakajima
   •  & MH Bachman

3. Department of Joint disease and Rheumatism, Nippon Medical School, Tokyo, Japan

   • A Nakajima

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