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Published on: August 16, 2019
Antigen-specific blockade of lethal CD8 T-cell mediated autoimmunity in a mouse model of multiple sclerosis
Shin-Young Na1, Heike Eujen, Kerstin Göbel
1Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
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.
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.
