In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 79, No. 1 ( 2005-10-21), p. 140-146
Abstract:
Systemic injection of small amounts of transforming growth factor-β (TGF-β), a cytokine produced by lymphoid and other cells, has a profound effect in protecting mice from the nflammatory demyelinating lesions of experimental allergic encephalomyelitis (EAE; an animal model for multiple sclerosis). However, TGF-β has side-effects, which might be avoided if the cells producing TGF-β 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-β. 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 TGF-β1-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-β1-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-β1-producing Th2 cells were detectable in the spinal cords of the injected mice.
Type of Medium:
Online Resource
ISSN:
1938-3673
,
0741-5400
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2005
detail.hit.zdb_id:
2026833-6
SSG:
12
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