title: Gammadelta T cells but not NK cells are essential for cell-mediated immunity against Plasmodium chabaudi malaria.
abstract: Blood-stage Plasmodium chabaudi infections are suppressed by antibody-mediated immunity and/or cell-mediated immunity (CMI). To determine the contributions of NK cells and γδ T cells to protective immunity, C57BL/6 (wild-type [WT]) mice and B-cell-deficient (J(H(-/-))) mice were infected with P. chabaudi and depleted of NK cells or γδ T cells with monoclonal antibody. The time courses of parasitemia in NK-cell-depleted WT mice and J(H(-/-)) mice were similar to those of control mice, indicating that deficiencies in NK cells, NKT cells, or CD8(+) T cells had little effect on parasitemia. In contrast, high levels of noncuring parasitemia occurred in J(H(-/-)) mice depleted of γδ T cells. Depletion of γδ T cells during chronic parasitemia in B-cell-deficient J(H(-/-)) mice resulted in an immediate and marked exacerbation of parasitemia, suggesting that γδ T cells have a direct killing effect in vivo on blood-stage parasites. Cytokine analyses revealed that levels of interleukin-10, gamma interferon (IFN-γ), and macrophage chemoattractant protein 1 (MCP-1) in the sera of γδ T-cell-depleted mice were significantly (P < 0.05) decreased compared to hamster immunoglobulin-injected controls, but these cytokine levels were similar in NK-cell-depleted mice and their controls. The time courses of parasitemia in CCR2(-/-) and J(H(-/-)) × CCR2(-/-) mice and in their controls were nearly identical, indicating that MCP-1 is not required for the control of parasitemia. Collectively, these data indicate that the suppression of acute P. chabaudi infection by CMI is γδ T cell dependent, is independent of NK cells, and may be attributed to the deficient IFN-γ response seen early in γδ T-cell-depleted mice.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA. wweidanz@wisc.edu
authors.forename: William P
authors.initials: WP
authors.lastname: Weidanz
authors.forename: GayeLyn
authors.initials: G
authors.lastname: LaFleur
authors.forename: Andrew
authors.initials: A
authors.lastname: Brown
authors.forename: James M
authors.initials: JM
authors.lastname: Burns
authors.forename: Irene
authors.initials: I
authors.lastname: Gramaglia
authors.forename: Henri C
authors.initials: HC
authors.lastname: van der Heyde
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology*; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018512:Parasitemia / Q000276:immunology; D016788:Plasmodium chabaudi; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D013997:Time Factors
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007074:Immunoglobulin G; D007371:Interferon-gamma