Participation of lymphocyte subpopulations in the pathogenesis of experimental murine cerebral malaria
| Autor: | D M, Yañez, D D, Manning, A J, Cooley, W P, Weidanz, H C, van der Heyde |
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| Rok vydání: | 1996 |
| Předmět: |
Mice
Knockout Plasmodium berghei Genes MHC Class II Histocompatibility Antigens Class II Malaria Cerebral Mice SCID CD8-Positive T-Lymphocytes Th1 Cells Lymphocyte Depletion Lymphocyte Subsets Interleukin-10 Specific Pathogen-Free Organisms Antigens Differentiation B-Lymphocyte Mice Inbred C57BL Immunocompromised Host Interferon-gamma Mice Th2 Cells Animals Interleukin-2 Female Severe Combined Immunodeficiency Interleukin-4 beta 2-Microglobulin |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 157(4) |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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