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PubMed · 9770517

Gene therapy in allergic encephalomyelitis using myelin basic protein-specific T cells engineered to express latent transforming growth factor-beta1.

L Z Chen·G M Hochwald·C Huang·G Dakin·H Tao·C Cheng·W J Simmons·G Dranoff·G J Thorbecke
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Abstract

A myelin basic protein (MBP)-specific BALB/c T helper 1 (Th1) clone was transduced with cDNA for murine latent transforming growth factor-beta1 (TGF-beta1) by coculture with fibroblasts producing a genetically engineered retrovirus. When SJL x BALB/c F1 mice, immunized 12-15 days earlier with proteolipid protein in complete Freund's adjuvant, were injected with 3 x 10(6) cells from MBP-activated untransduced cloned Th1 cells, the severity of experimental allergic encephalomyelitis (EAE) was slightly increased. In contrast, MBP-activated (but not resting) latent TGF-beta1-transduced T cells significantly delayed and ameliorated EAE development. This protective effect was negated by simultaneously injected anti-TGF-beta1. The transduced cells secreted 2-4 ng/ml of latent TGF-beta1 into their culture medium, whereas control cells secreted barely detectable amounts. mRNA profiles for tumor necrosis factor, lymphotoxin, and interferon-gamma were similar before and after transduction; interleukin-4 and -10 were absent. TGF-beta1-transduced and antigen-activated BALB/c Th1 clones, specific for hemocyanin or ovalbumin, did not ameliorate EAE. Spinal cords from mice, taken 12 days after receiving TGF-beta1-transduced, antigen-activated cells, contained detectable amounts of TGF-beta1 cDNA. We conclude that latent TGF-beta1-transduced, self-reactive T cell clones may be useful in the therapy of autoimmune diseases.

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AnimalsAntibodies, MonoclonalAntigen-Antibody ReactionsBase SequenceCarrier ProteinsClone CellsCrosses, GeneticDNA PrimersEncephalomyelitis, Autoimmune, ExperimentalFemaleGenetic TherapyIntracellular Signaling Peptides and ProteinsLatent TGF-beta Binding ProteinsMaleMiceMice, Inbred BALB CMyelin Basic ProteinT-LymphocytesJournal ArticleResearch Support, Non-U.S. Gov't

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L Z Chen, G M Hochwald, C Huang, G Dakin, H Tao, C Cheng, W J Simmons, G Dranoff, G J Thorbecke. 1998-10-13. Gene therapy in allergic encephalomyelitis using myelin basic protein-specific T cells engineered to express latent transforming growth factor-beta1.. https://doi.org/10.1073/pnas.95.21.12516

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