Abstract
To investigate CD8+ regulatory T cell influence on multiple sclerosis development, peripheral blood and cerebrospinal fluid (CSF) CD8+ T cell clones (TCCs) recognizing MBP(83-102) and MOG(63-87)-specific CD4+ T cells were isolated from 20 patients during acute exacerbations, 15 in remission and 15 controls. Blood and CSF CD8+ regulatory TCC cloning frequency decreased more during exacerbations than remissions or controls. Target cell pre-activation significantly enhanced CD8+ T granule-mediated cell killing of CD4+ targets, and was restricted by HLA-E. During exacerbations, killer-inhibitory receptor CD94/NKG2A expression was significantly higher in CD8+ TCCs, limiting their cytotoxic activity. Moreover, IL-15 and IFN-gamma significantly increased CD94 and NKG2A expression. These data provide evidence that CD94/NKG2A receptors play an important role in regulating T cell activity during the course of MS.
MeSH terms
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Adult
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CD28 Antigens / metabolism
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism*
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Cell Proliferation
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Cells, Cultured
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Cytokines / metabolism
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Female
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Flow Cytometry
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Granzymes / pharmacology
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Humans
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Lymphocyte Activation / drug effects
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Male
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Middle Aged
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Multiple Sclerosis, Relapsing-Remitting / pathology*
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Myelin Basic Protein / pharmacology
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NK Cell Lectin-Like Receptor Subfamily C
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NK Cell Lectin-Like Receptor Subfamily D / metabolism
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Peptide Fragments / pharmacology
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Perforin / pharmacology
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Receptors, Immunologic / metabolism
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Receptors, Natural Killer Cell
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism*
Substances
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CD28 Antigens
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Cytokines
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KLRC1 protein, human
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Myelin Basic Protein
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NK Cell Lectin-Like Receptor Subfamily C
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NK Cell Lectin-Like Receptor Subfamily D
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Peptide Fragments
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Receptors, Immunologic
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Receptors, Natural Killer Cell
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Perforin
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Granzymes