Abstract
Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is primarily mediated by CD4 T cells specific for Ags in the CNS. Using MHC class II tetramers, we assessed expansion and phenotypic differentiation of polyclonal self-reactive CD4 T cells during EAE after primary and secondary challenge with the specific Ag. After EAE induction in SJL mice with proteolipid protein 139-151, CNS-specific T cells up-regulated activation markers and expanded in the draining lymph nodes and in the spleen. Less than 20% of total autoreactive T cells entered the CNS simultaneously with Th cells of other specificities. Almost all tetramer-positive cells in the CNS were activated and phenotypically distinct from the large peripheral pool. When EAE was induced in Ag-experienced mice, disease symptoms developed earlier and persisted longer; autoreactive T cells were more rapidly activated and invaded the CNS earlier. In striking contrast to specific CTLs that respond after secondary viral challenge, the absolute numbers of autoreactive CD4 T cells were not increased, indicating that the accelerated autoreactivity in Ag-experienced mice is not related to higher frequencies of autoreactive CD4 T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoantigens / immunology*
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Autoantigens / metabolism
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism*
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Cell Differentiation / immunology
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Cell Division / immunology
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Central Nervous System / immunology
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Central Nervous System / pathology
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Epitopes, T-Lymphocyte / immunology
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Female
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Freund's Adjuvant / administration & dosage
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Freund's Adjuvant / immunology
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Histocompatibility Antigens Class II / immunology
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Histocompatibility Antigens Class II / metabolism*
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Immunization
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Immunization, Secondary
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Immunophenotyping
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Lymphocyte Activation
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Lymphocyte Count
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Mice
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Myelin Proteins
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Myelin Proteolipid Protein / administration & dosage*
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Myelin Proteolipid Protein / immunology
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Myelin Proteolipid Protein / metabolism
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Myelin-Associated Glycoprotein / administration & dosage*
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Myelin-Associated Glycoprotein / immunology
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Myelin-Associated Glycoprotein / metabolism
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments / administration & dosage*
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
Substances
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Autoantigens
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class II
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Mog protein, mouse
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Myelin Proteins
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Myelin Proteolipid Protein
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Myelin-Associated Glycoprotein
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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myelin proteolipid protein (139-151)
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Freund's Adjuvant