Abstract
Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis characterized by infiltration of activated CD4(+) T lymphocytes into tissues of the CNS. This study investigated the role of CD43 in the induction and progression of EAE. Results demonstrate that CD43-deficient mice have reduced and delayed clinical and histological disease severity relative to CD43(+/+) mice. This reduction was characterized by decreased CD4(+) T cell infiltration of the CNS of CD43(-/-) mice but similar numbers of Ag-specific T cells in the periphery, suggesting a defect in T cell trafficking to the CNS. The absence of CD43 also affected cytokine production, as myelin oligodendrocyte glycoprotein (MOG) 35-55-specific CD43(-/-) CD4(+) T cells exhibited reduced IFN-gamma and increased IL-4 production. CD43(-/-) CD4(+) MOG-primed T cells exhibited reduced encephalitogenicity relative to CD43(+/+) cells upon adoptive transfer into naive recipients. These results suggest a role for CD43 in the differentiation and migration of MOG(35-55)-specific T cells in EAE, and identify it as a potential target for therapeutic intervention.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / deficiency
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Adjuvants, Immunologic / genetics
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Adjuvants, Immunologic / physiology*
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Adoptive Transfer
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Amino Acid Sequence
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Animals
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Antigens, CD*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / pathology
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CD4-Positive T-Lymphocytes / transplantation
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Cell Movement / genetics
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Cell Movement / immunology
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Cells, Cultured
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Cytokines / biosynthesis
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Disease Progression
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Down-Regulation / genetics
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Down-Regulation / immunology
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology*
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Encephalomyelitis, Autoimmune, Experimental / prevention & control
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Epitopes, T-Lymphocyte / immunology
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Glycoproteins / immunology
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Incidence
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Leukosialin
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, SCID
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Molecular Sequence Data
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments / immunology
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Severity of Illness Index
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Sialoglycoproteins / deficiency
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Sialoglycoproteins / genetics
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Sialoglycoproteins / physiology*
Substances
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Adjuvants, Immunologic
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Antigens, CD
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Cytokines
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Epitopes, T-Lymphocyte
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Glycoproteins
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Leukosialin
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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Sialoglycoproteins
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Spn protein, mouse
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myelin oligodendrocyte glycoprotein (35-55)