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

Immunity. 2003 Mar;18(3):391-402. doi: 10.1016/s1074-7613(03)00052-9.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens / metabolism
  • Antigens, CD1 / genetics
  • Antigens, CD1 / metabolism*
  • Antigens, CD1d
  • Antigens, Surface
  • Cytokines / biosynthesis
  • Killer Cells, Natural / immunology*
  • Lectins, C-Type
  • Malaria, Cerebral / etiology
  • Malaria, Cerebral / genetics
  • Malaria, Cerebral / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NK Cell Lectin-Like Receptor Subfamily B
  • Plasmodium berghei
  • Proteins / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • T-Lymphocyte Subsets / immunology*
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Antigens
  • Antigens, CD1
  • Antigens, CD1d
  • Antigens, Surface
  • Cytokines
  • Lectins, C-Type
  • NK Cell Lectin-Like Receptor Subfamily B
  • Proteins
  • Receptors, Antigen, T-Cell, alpha-beta