Latent TGF- 1-transduced CD4 T cells suppress the progression of allergic encephalomyelitis

Systemic injection of small amounts of transforming growth factor(TGF), a cytokine produced by lymphoid and other cells, has a profound effect in protecting mice from the inflammatory demyelinating lesions of experimental allergic encephalomyelitis (EAE; an animal model for multiple sclerosis). However, TGFhas side-effects, which might be avoided if the cells producing TGFcan be delivered to the affected site in the nervous system to insure its local release in small amounts. Myelin basic protein (MBP)-specific, cloned CD4 T cells were engineered by retroviral transduction to produce latent TGF. Studies about the spontaneous form of EAE in T cell receptor (TCR)-transgenic recombination-activating gene (RAG)-1 / mice showed that essentially all of the MBP-specific, TCR-transgenic RAG-1 / (BALB/c B10.PL)F1 mice develop spontaneous EAE by the age of 11 weeks. By 12 weeks, 25–50% of the mice have died from disease. A single injection of TGF1-transduced T helper cell type 1 (Th1) cells significantly protected the mice from EAE, and untransduced Th1 cells did not protect. MBP-specific BALB/c Th2 clones, transduced with TGF1-internal ribosome entry site-green fluorescent protein (GFP) significantly reduced EAE induction by untransduced Th1 cells in RAG-1 / B10.PL mice. Furthermore, the GFP TGF1-producing Th2 cells were detectable in the spinal cords of the injected mice. J. Leukoc. Biol. 79: 140–146; 2006.