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Retrovirally-engineered antigen-specific T cells home to the inflamed joints and suppress collagen-induced arthrtis
Arthritis Research & Therapy volume 3, Article number: P37 (2001)
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.
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Nakajima, A., Seroogy, C., Sandora, M. et al. Retrovirally-engineered antigen-specific T cells home to the inflamed joints and suppress collagen-induced arthrtis. Arthritis Res Ther 3, P37 (2001). https://doi.org/10.1186/ar364
- Local Delivery
- Inflame Joint
- Primary Immunization
- Cell Home
- Promising Therapeutic Strategy