Abstract |
Hematopoietic stem cell (HSC) transplantation is a potential therapy that can offer multiple sclerosis patients a radical, potentially curative treatment. Using experimental autoimmune encephalomyelitis (EAE) as a model, we previously reported that retrovirally transduced B cells expressing myelin basic protein (MBP), MBP Ac1-11, or myelin oligodendrocyte glycoprotein p35-55 induced tolerance and reduced symptoms. Here, we extend our tolerance approach using bone marrow (BM) cells expressing full-length phospholipid protein (PLP) in a model for relapsing, remitting EAE. Using GFP expression as a marker, we found that up to 50% of cells were positive for transgene expression in peripheral blood after 900 rad irradiation and transduced BM transplantation, and expression was stable in hematopoietic lineages for over 10 weeks. Upon challenge, T cell proliferation in response to PLP p139-151 was reduced and EAE was completely abolished in a pretreatment protocol. In addition, protection from EAE could be achieved with PLP-transduced BM cells given on day 12 after immunization, a potential therapeutic protocol. Finally, the protective effect of PLP-expressing BM could also be observed using a nonmyeloablative protocol, albeit with lower efficacy. Our results suggest that HSC may be useful to achieve long-lasting tolerance to protect mice from EAE and possibly to promote CNS repair in ongoing EAE.
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Authors | Biying Xu, Peter Haviernik, Lawrence A Wolfraim, Kevin D Bunting, David W Scott |
Journal | Molecular therapy : the journal of the American Society of Gene Therapy
(Mol Ther)
Vol. 13
Issue 1
Pg. 42-8
(Jan 2006)
ISSN: 1525-0016 [Print] United States |
PMID | 16219491
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- CD4 Antigens
- Myelin Proteolipid Protein
- Peptide Fragments
- Receptors, Interleukin-2
- myelin proteolipid protein (139-151)
- L-Selectin
- Green Fluorescent Proteins
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Topics |
- Animals
- Bone Marrow Cells
(metabolism)
- Bone Marrow Transplantation
- CD4 Antigens
(immunology)
- Cell Proliferation
- Combined Modality Therapy
- Encephalomyelitis, Autoimmune, Experimental
(immunology, radiotherapy, therapy)
- Female
- Genetic Therapy
- Genetic Vectors
- Green Fluorescent Proteins
(genetics)
- Humans
- Immune Tolerance
- Immunization
- L-Selectin
(immunology)
- Mice
- Myelin Proteolipid Protein
(genetics, immunology, metabolism)
- Peptide Fragments
(genetics, immunology, metabolism)
- Receptors, Interleukin-2
(immunology)
- T-Lymphocytes
(immunology, pathology)
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