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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.