RRC ID 4783
Author Nakajima A, Seroogy CM, Sandora MR, Tarner IH, Costa GL, Taylor-Edwards C, Bachmann MH, Contag CH, Fathman CG.
Title Antigen-specific T cell-mediated gene therapy in collagen-induced arthritis.
Journal J Clin Invest
Abstract 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-specific (CII-specific) CD4(+) T hybridomas or primary CD4(+) T cells after gene transfer, as vehicles to deliver an immunoregulatory protein for the treatment of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). CII-specific T cells or hybridomas were transduced using retroviral vectors to constitutively express the IL-12 antagonist, IL-12 p40. Transfer of engineered CD4(+) T cells after immunization significantly inhibited the development of CIA, while cells transduced with vector control had no effect. The beneficial effect on CIA of IL-12 p40-transduced T cells required TCR specificity against CII, since transfer of T cells specific for another antigen producing equivalent amounts of IL-12 p40 had no effect. In vivo cell detection using bioluminescent labels and RT-PCR showed that transferred CII-reactive T-cell hybridomas accumulated in inflamed joints in mice with CIA. These results indicate that the local delivery of IL-12 p40 by T cells inhibited CIA by suppressing autoimmune responses at the site of inflammation. Modifying antigen-specific T cells by retroviral transduction for local expression of immunoregulatory proteins thus offers a promising strategy for treating RA.
Volume 107(10)
Pages 1293-301
Published 2001-5-1
DOI 10.1172/JCI12037
PMID 11375419
PMC PMC209299
MeSH Adoptive Transfer Animals Arthritis, Rheumatoid / therapy* Collagen / immunology* Genetic Therapy / methods* Hybridomas Interleukin-12 / antagonists & inhibitors Male Mice Mice, Inbred DBA Retroviridae / genetics T-Lymphocyte Subsets / immunology* T-Lymphocyte Subsets / transplantation
IF 12.282
Times Cited 141
DNA material pMFGmIL12p40 (RDB1447)