title: Cytokine profile of Plasmodium falciparum-specific T cells in non-immune malaria patients.
abstract: CD3+ T cells are important sources of both pro- and anti-inflammatory cytokines during Plasmodium falciparum malaria. We studied the frequency of interleukin-2 (IL-2), gamma interferon (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-10 expressing CD3+ cells in 10 non-immune malaria patients with uncomplicated malaria and in one patient with cerebral malaria after P. falciparum-specific and non-specific mitogenic stimulation. Analysis by fluorescence-activated cell sorting was performed after drug-induced clearance of parasites to allow previously sequestered T cells to be detected in peripheral blood. CD3+ cells of patients responded to P. falciparum infected erythrocytes with significant increases in the percentage of IL-2, IFN-gamma, and TNF-alpha, but also IL-10, positive cells. CD3+ cells from malaria-naïve donors were also responsive to specific stimulation albeit to a much lesser extent. Mitogenic stimulation of PBMC revealed no significant differences between cells of patients and controls. CD3+ cells of the patient with cerebral malaria were hyporesponsive both to the infecting parasite isolate as well as to our laboratory-adapted P. falciparum isolate, whereas two patients with uncomplicated disease were more responsive to their infecting parasites than to the laboratory-adapted isolate. The results indicate that the increased responsiveness of in vivo primed compared to malaria-naïve CD3+ cells is Plasmodium-specific and biased towards production of IFN-gamma and TNF-alpha.
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases, University of Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Ramharter
authors.forename: Martin
authors.initials: M
authors.lastname: Willheim
authors.forename: Heidi
authors.initials: H
authors.lastname: Winkler
authors.forename: Katharina
authors.initials: K
authors.lastname: Wahl
authors.forename: Heimo
authors.initials: H
authors.lastname: Lagler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Graninger
authors.forename: Stefan
authors.initials: S
authors.lastname: Winkler
mesh_terms: D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage; D017252:CD3 Complex / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016779:Malaria, Cerebral / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000953:Antigens, Protozoan; D017252:CD3 Complex; D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma