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Immunity. 2003 Mar;18(3):391-402.

Regulation of murine cerebral malaria pathogenesis by CD1d-restricted NKT cells and the natural killer complex.

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The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.


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.

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