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Published online before print October 21, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0505271

Received for publication May 17, 2005.
Revised August 5, 2005.
Accepted for publication August 17, 2005.

Article

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

Mitsuyuki Murano ^*, Xiaozhong Xiong ^*, Naoko Murano ^*, James L. Salzer , Juan J. Lafaille ^*, and Vincent K. Tsiagbe ^*@

Departments of *Pathology and NYU Cancer Institute and Cell Biology, New York University School of Medicine, New York

^@ To whom correspondence should be addressed. E-mail: tsiagv01{at}med.nyu.edu.

	Abstract

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, TGF- has side-effects, which might be avoided if the cells producing TGF- can 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/cxB10.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 TGF-1-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 TGF-1-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⁺ TGF-1-producing Th2 cells were detectable in the spinal cords of the injected mice.

Key Words: cytokines • gene therapy • multiple sclerosis