Tolerance induction by bone marrow transplantation in a multiple sclerosis model.
Experimental autoimmune encephalomyelitis (EAE) in rats is a highly valuable model of multiple sclerosis (MS) because it mimics major hallmarks of the human disease. EAE induced with myelin-oligodendrocyte-glycoprotein (MOG) in DA rats is relapsing/remitting, and lesions in the central nervous system show inflammation, demyelination, and axonal and neuronal loss. Recently, bone marrow transplantation (BMT) was introduced as a novel strategy to treat MS, but its efficiency and the underlying mechanism are debatable. In MOG-induced EAE we found that BMT at the peak of EAE but not in the chronic phase leads to disease attenuation. In both settings, rats receiving bone marrow (BM) transplants were protected from subsequently induced relapses. These findings could be confirmed by histopathology in which rats receiving BM transplants did not have lesions compared with controls not receiving transplants. Importantly, the protective effect was achieved by allogeneic, syngeneic, and BM grafts from diseased rats. BMT resulted in increased numbers of CD4(+)CD25(bright) regulatory T cells, increased Foxp3 expression, a shift in T-cell epitope recognition, and a strong reduction of autoantibodies even after rechallenge with MOG. Thus, our results indicate potential mechanisms of how BMT may contribute to the improvement of MS and provide a rationale for its application in patients suffering from various autoimmune diseases.
Herrmann
Martin M
MM
Hertie Institute for Clinical Brain Research, Department of General Neurology, Experimental Neuroimmunology Laboratory, University of Tübingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
Gaertner
Susanne
S
Stadelmann
Christine
C
van den Brandt
Jens
J
Böscke
Robert
R
Budach
Wilfried
W
Reichardt
Holger M
HM
Weissert
Robert
R
D000818:Animals; D001323:Autoantibodies / Q000494:pharmacology; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D007108:Immune Tolerance; D008214:Lymphocytes / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010641:Phenotype; D051381:Rats; D011912:Rats, Inbred ACI; D011919:Rats, Inbred Strains; D012008:Recurrence; D013997:Time Factors
D001323:Autoantibodies; C571326:MOG protein, human; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein