Abstract
NKT cells are specialized cells coexpressing NK and T cell receptors. Upon activation they rapidly produce high levels of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) and are therefore postulated to influence T(H)1/T(H)2 immune responses. The precise role of the CD1/NKT cell pathway in immune response to infection remains unclear. We show here that CD1d-restricted NKT cells from distinct genetic backgrounds differentially influence T(H)1/T(H)2 polarization, proinflammatory cytokine levels, pathogenesis, and fatality in the P. berghei ANKA/rodent model of cerebral malaria. The functional properties of CD1d-restricted NKT cells vary according to expression of loci of the natural killer complex (NKC) located on mouse chromosome 6, which is shown here to be a significant genetic determinant of murine malarial fatalities.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens / metabolism
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Antigens, CD1 / genetics
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Antigens, CD1 / metabolism*
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Antigens, CD1d
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Antigens, Surface
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Cytokines / biosynthesis
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Killer Cells, Natural / immunology*
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Lectins, C-Type
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Malaria, Cerebral / etiology
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Malaria, Cerebral / genetics
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Malaria, Cerebral / immunology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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NK Cell Lectin-Like Receptor Subfamily B
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Plasmodium berghei
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Proteins / metabolism
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
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T-Lymphocyte Subsets / immunology*
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Th1 Cells / immunology
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Th2 Cells / immunology
Substances
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Antigens
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Antigens, CD1
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Antigens, CD1d
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Antigens, Surface
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Cytokines
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Lectins, C-Type
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NK Cell Lectin-Like Receptor Subfamily B
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Proteins
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Receptors, Antigen, T-Cell, alpha-beta