Regulation of Murine Cerebral Malaria Pathogenesis by CD1d-Restricted NKT Cells and the Natural Killer Complex

Abstract NKT cells are specialized cells coexpressing NK and T cell receptors. Upon activation they rapidly produce high levels of interferon-γ (IFN-γ) 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.