Participation of lymphocyte subpopulations in the pathogenesis of experimental murine cerebral malaria

J Immunol. 1996 Aug 15;157(4):1620-4.


We determined the requirement for selected lymphocyte subsets and cytokines in the pathogenesis of experimental murine cerebral malaria (CM) by using gene-targeted knockout and mAb-suppressed mice. Plasmodium berghei ANKA infection induced CM in A 0/0 mice, which lack expression of surface MHC class II glycoproteins and consequently express a severe and chronic reduction in numbers of CD4+ T cells. However, when A 0/0 mice, which are on a C57BL/6 x 129 genetic background, or immune-intact C57BL/6 controls treated with anti-CD4 mAb were infected, none developed CM. The latter finding confirms an earlier report that CD4+ T cells are required for CM to occur and additionally indicates that the reduced numbers of CD4+ T cells present in A 0/0 mice are sufficient for CM development. Neither the recently described CD4+, NK1.1+ T cell subset shown to be present in A 0/0 mice nor traditional NK cells seem to be required for the induction of CM because A 0/0 and C57BL/6 mice severely depleted of both NK1.1+ populations with mAb developed CM as readily as did normal Ig-treated controls. Deficiency of Th1-associated cytokines (IFN-gamma or IL-2) in mice by gene-targeted disruptions completely inhibited CM development, whereas the lack of Th2-associated cytokines (IL-4 or IL-10) did not prevent this disease. Our observation that B cell-deficient JHD and microMT mice developed CM provides evidence that neither B cells, their products, nor B cell Ag presentation are a requisite for CM pathology. We further observed that neither beta 2m 0/0 knockout mice, which lack CD8+ alpha beta T cells, nor C57BL/6 mice depleted of CD8+ T cells with anti-CD8 mAb treatment developed CM, leading us to conclude that CD8+ T cells are also crucial for the development of CM.

Publication types

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

MeSH terms

  • Animals
  • Antigens, Differentiation, B-Lymphocyte / genetics
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Genes, MHC Class II
  • Histocompatibility Antigens Class II / genetics
  • Immunocompromised Host
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interferon-gamma / physiology*
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-2 / deficiency
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Interleukin-2 / physiology*
  • Interleukin-4 / deficiency
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Lymphocyte Depletion
  • Lymphocyte Subsets / immunology
  • Malaria, Cerebral / complications
  • Malaria, Cerebral / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, SCID
  • Plasmodium berghei*
  • Severe Combined Immunodeficiency / complications
  • Specific Pathogen-Free Organisms
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • beta 2-Microglobulin / deficiency
  • beta 2-Microglobulin / genetics


  • Antigens, Differentiation, B-Lymphocyte
  • Histocompatibility Antigens Class II
  • Interleukin-2
  • beta 2-Microglobulin
  • invariant chain
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma