Bone marrow transplantation combined with gene therapy to induce antigen-specific tolerance and ameliorate EAE

Biying Xu, Peter Haviernik, Lawrence A. Wolfraim, Kevin D. Bunting, David W. Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish
Pages (from-to)42-48
Number of pages7
JournalMolecular Therapy
Issue number1
StatePublished - Jan 2006
Externally publishedYes


  • Autoimmune disease
  • Bone marrow transplantation
  • Gene therapy


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