1. ¹Department of Surgery and Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201, USA
2. ²Division of Hematology/Oncology, Case Western Reserve University, Cleveland, OH 44106, USA
3. ³Tolergenics, Inc., Rockville, MD 20850, USA
4. ⁴Center for Stem Cell and Regenerative Medicine, Cleveland, OH 44106, USA

Correspondence: David W. Scott, Fax: +1 410 706 8234. E-mail: davscott@som.umaryland.edu

Received 2 September 2005; Revised 2 September 2005; Accepted 2 September 2005.

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.