Browsing by Author "Rott, E."

There is accumulating evidence that CD8-positive (CD8(+)) T-cells and MHC-I expression may also play a role in neurodegeneration associated with multiple sclerosis (MS). We investigated the role of MHC-I and CD8(+) T-cells by studying experimental autoimmune encephalomyelitis (EAE) in beta-2 microglobulin knockout mice induced by myelin oligodendrocyte glycoprotein (MOG) peptide 3555 or whole rat myelin basic protein (rMBP). For both encephalitogens and even after reconstitution of the immune system with MHC-I-positive bone marrow and transfer of mature CD8(+) T-cells (iMHC-I+ CD8(+) beta 2m-/- mice), the disease course in beta m-/- mice was significantly more severe with a 10-fold increased mortality in the beta 2m-/- mice as compared to wild-type C57BL/6 mice. EAE in beta 2m-/- mice caused more severe demyelination after immunization with MOG than with rMBP and axonal damage was more marked with rMBP as well as MOG even in iMHC-I+ CD8(+) beta 2m-/- mice. Immunocytochemical analysis of spinal cord tissue revealed a significant increase in macrophage and microglia infiltration in 2m-/- and iMHC-I+ CD8' 2m-/- mice. The different pattern of T-cell infiltration was underscored by a 2.5-fold increase in CD4-positive (CD4(+)) T-cells in beta 2m-/- mice after induction of MOG 35-55 EAE. We conclude that lack of functional MHC-I molecules and CD8+ T-cells aggravates autoimmune tissue destruction in the CNS. Enhanced axonal damage speaks for pathways of tissue damage independent of CD8(+) T-cells and neuronal NIHC-I expression. (c) 2005 Elsevier Inc. All rights reserved.