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

• Published in: The Journal of immunology (1950) Vol. 157; no. 4; pp. 1620 - 1624
• Main Authors: Yanez, DM, Manning, DD, Cooley, AJ, Weidanz, WP, van der Heyde, HC
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.08.1996
• Subjects: AIDS/HIV; Animals; Antigens, Differentiation, B-Lymphocyte - genetics; beta 2-Microglobulin - deficiency; beta 2-Microglobulin - 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 - physiology; Interferon-gamma - secretion; Interleukin-10 - deficiency; Interleukin-10 - genetics; Interleukin-10 - secretion; Interleukin-2 - deficiency; Interleukin-2 - genetics; Interleukin-2 - physiology; Interleukin-2 - secretion; Interleukin-4 - deficiency; Interleukin-4 - genetics; Interleukin-4 - secretion; 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 - secretion; Th2 Cells - immunology; Th2 Cells - secretion
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.157.4.1620

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.