title: Participation of lymphocyte subpopulations in the pathogenesis of experimental murine cerebral malaria.
abstract: 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.
authors: Department of Medical Microbiology and Immunology, University of Wisconsin, Madison 53706, USA.
authors: D M
authors: DM
authors: Yañez
authors: D D
authors: DD
authors: Manning
authors: A J
authors: AJ
authors: Cooley
authors: W P
authors: WP
authors: Weidanz
authors: H C
authors: HC
authors: van der Heyde
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology; D016779:Malaria, Cerebral / Q000150:complications / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D010962:Plasmodium berghei; D016511:Severe Combined Immunodeficiency / Q000150:complications; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D001613:beta 2-Microglobulin; C045084:invariant chain; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma