Linked Life Data

17531772

Source:http://linkedlifedata.com/resource/pubmed/id/17531772

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-5-28
pubmed:abstractText
Autologous hematopoietic stem cell transplantation (HSCT) is being explored in the treatment of severe multiple sclerosis (MS), and is based on the concept of "resetting" the immune system. The use of allogeneic HSCT may offer additional advantages, such as the replacement of the autoreactive immune compartment by healthy allogeneic cells and development of a graft-versus-autoimmunity (GVA) effect. However, in clinical practice, the genetic susceptibility to MS of allogeneic stem cell donors is generally unknown, and GVA may therefore be an important mechanism of action. Experimental autoimmune encephalomyelitis (EAE)-susceptible and -resistant mouse strains were used to determine the roles of genetic susceptibility, level of donor-chimerism, and alloreactivity in the therapeutic potential of syngeneic versus allogeneic bone marrow transplant (BMT) for EAE. After transplantation and EAE induction, animals were evaluated for clinical EAE and ex vivo myelin oligodendrocyte glycoprotein-specific proliferation. Early after BMT, both syngeneic and allogeneic chimeras were protected from EAE development. On the longer term, allogeneic but not syngeneic BMT conferred protection, but this required high-level donor-chimerism from EAE-resistant donors. Importantly, when EAE-susceptible donors were used, robust protection from EAE was obtained when active alloreactivity, induced by donor lymphocyte infusions, was provided. Our findings indicate the requirement of a sufficient level of donor-chimerism from a nonsusceptible donor in the therapeutic effect of allogeneic BMT. Importantly, the data indicate that, independently of genetic susceptibility, active alloreactivity is associated with a GVA effect, thereby providing new evidence to support the potential role of allogeneic BMT in the treatment of MS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1083-8791
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
627-37
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Allogeneic bone marrow transplantation in models of experimental autoimmune encephalomyelitis: evidence for a graft-versus-autoimmunity effect.
pubmed:affiliation
Laboratory of Experimental Transplantation, University of Leuven, Leuven, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't