Antigen-specific blockade of lethal CD8 T-cell mediated autoimmunity in a mouse model of multiple sclerosis.
Increasing evidence implies CD8 T cells in tissue-specific autoimmune diseases including multiple sclerosis. mAbs specific for MHC class I molecules presenting a dominant autoantigenic peptide may allow selective immunotherapy in such settings. We demonstrate the prophylactic and therapeutic efficacy of such a mAb in a transgenic mouse model of lethal demyelinating disease in which a neo-self Ag expressed by oligodendrocytes is targeted by CD8 T cells with transgenic Ag receptors. Mechanistic studies performed in vitro and in vivo indicate that it is the low expression of MHC class I on oligodendrocytes, which makes this form of Ag-specific intervention possible.
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
Shin-Young
SY
Na
Heike
H
Eujen
Kerstin
K
Göbel
Sven G
SG
Meuth
Kati
K
Martens
Heinz
H
Wiendl
Thomas
T
Hünig
D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009103:Multiple Sclerosis / Q000276:immunology*; D009836:Oligodendroglia / Q000276:immunology; D010047:Ovalbumin / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D001324:Autoantigens; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin