PMID- 19277013
OWN - NLM
STAT- MEDLINE
DCOM- 20090629
LR  - 20211109
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 17
IP  - 5
DP  - 2009 May
TI  - Tolerance induction in experimental autoimmune encephalomyelitis using 
      non-myeloablative hematopoietic gene therapy with autoantigen.
PG  - 897-905
LID - 10.1038/mt.2009.42 [doi]
AB  - Experimental autoimmune encephalomyelitis (EAE) constitutes a paradigm of antigen 
      (Ag)-specific T cell driven autoimmune diseases. In this study, we transferred 
      bone marrow cells (BMCs) expressing an autoantigen (autoAg), the peptide 40-55 of 
      the myelin oligodendrocytic glycoprotein (MOG(40-55)), to induce preventive and 
      therapeutic immune tolerance in a murine EAE model. Transfer of BMC expressing 
      MOG(40-55) (IiMOG-BMC) into partially myeloablated mice resulted in molecular 
      chimerism and in robust protection from the experimental disease. In addition, in 
      mice with established EAE, transfer of transduced BMC with or without partial 
      myeloablation reduced the clinical and histopathological severity of the disease. 
      In these experiments, improvement was observed even in the absence of engraftment 
      of the transduced hematopoietic cells, probably rejected due to the previous 
      immunization with the autoAg. Splenocytes from mice transplanted with IiMOG-BMC 
      produced significantly higher amounts of interleukin (IL)-5 and IL-10 upon autoAg 
      challenge than those of control animals, suggesting the participation of 
      regulatory cells. Altogether, these results suggest that different tolerogenic 
      mechanisms may be mediating the preventive and the therapeutic effects. In 
      conclusion, this study demonstrates that a cell therapy using BMC expressing an 
      autoAg can induce Ag-specific tolerance and ameliorate established EAE even in a 
      nonmyeloablative setting.
FAU - Eixarch, Herena
AU  - Eixarch H
AD  - Centre de Teixits i Terapia Cel.lular, Banc de Sang i Teixits, Institut de 
      Recerca Hospital Universitari Vall d'Hebron, Barcelona, Spain.
FAU - Espejo, Carmen
AU  - Espejo C
FAU - Gomez, Alba
AU  - Gomez A
FAU - Mansilla, Maria Jose
AU  - Mansilla MJ
FAU - Castillo, Mireia
AU  - Castillo M
FAU - Mildner, Alexander
AU  - Mildner A
FAU - Vidal, Francisco
AU  - Vidal F
FAU - Gimeno, Ramon
AU  - Gimeno R
FAU - Prinz, Marco
AU  - Prinz M
FAU - Montalban, Xavier
AU  - Montalban X
FAU - Barquinero, Jordi
AU  - Barquinero J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090310
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Autoantigens)
RN  - 0 (Interleukin-5)
RN  - 0 (Myelin-Associated Glycoprotein)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
EIN - Mol Ther. 2009 Jul;17(7):1303
EIN - Mol Ther. 2009 Jul;17(7):1303. PMID: 28178479
MH  - Animals
MH  - Autoantigens/*immunology
MH  - Bone Marrow Cells
MH  - Bone Marrow Transplantation
MH  - Encephalomyelitis, Autoimmune, Experimental/*immunology/*therapy
MH  - Female
MH  - Flow Cytometry
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors
MH  - Immune Tolerance/*immunology
MH  - Interleukin-10/metabolism
MH  - Interleukin-5/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myelin-Associated Glycoprotein/immunology
MH  - Retroviridae
PMC - PMC2835141
EDAT- 2009/03/12 09:00
MHDA- 2009/06/30 09:00
PMCR- 2010/05/01
CRDT- 2009/03/12 09:00
PHST- 2009/03/12 09:00 [entrez]
PHST- 2009/03/12 09:00 [pubmed]
PHST- 2009/06/30 09:00 [medline]
PHST- 2010/05/01 00:00 [pmc-release]
AID - S1525-0016(16)31790-7 [pii]
AID - 10.1038/mt.2009.42 [doi]
PST - ppublish
SO  - Mol Ther. 2009 May;17(5):897-905. doi: 10.1038/mt.2009.42. Epub 2009 Mar 10.