title: Plasmodium falciparum infection of the placenta impacts on the T helper type 1 (Th1)/Th2 balance of neonatal T cells through CD4(+)CD25(+) forkhead box P3(+) regulatory T cells and interleukin-10.
abstract: Placental malaria infection affects the T helper type 1 (Th1)/Th2 balance in neonatal children. We investigated a potential role of regulatory T cells in this balance by comparing T cell responses of cord blood mononuclear cells (CBMC) from parasitized and non-parasitized placenta of Gambian women. CBMC were depleted of CD4(+)CD25(+) forkhead box P3 (FoxP3)(+) regulatory T cells and analysed in vitro for their ability to produce interferon (IFN)-gamma, sCD30 and interleukin (IL)-10 in response to phytohaemagglutinin (PHA), live Plasmodium falciparum, schizont extracts and the recombinant P. falciparum blood stage antigen merozoite surface protein 1 (MSP1(19)). As expected, lower IFN-gamma and higher sCD30 responses were observed for the cells from the parasitized group. In addition, higher IL-10 levels were produced by CBMC from the parasitized group. Depletion of regulatory T cells decreased IL-10 production, which resulted in a restoration of IFN-gamma expression in response to all stimuli. The Th2 marker sCD30 remained significantly higher in the parasitized group in response to malaria protein antigens while similar levels were recovered between both groups in response to live P. falciparum. Similar effects were observed by adding an antibody that blocks IL-10 function. These results suggest that the impact of P. falciparum infection on Th1 differentiation of neonatal T cells can be ascribed to regulatory T cells through production of IL-10.
authors.affiliation: Medical Research Council Laboratories, Banjul, The Gambia.
authors.forename: C
authors.initials: C
authors.lastname: Bisseye
authors.forename: M
authors.initials: M
authors.lastname: van der Sande
authors.forename: W D
authors.initials: WD
authors.lastname: Morgan
authors.forename: A A
authors.initials: AA
authors.lastname: Holder
authors.forename: M
authors.initials: M
authors.lastname: Pinder
authors.forename: J
authors.initials: J
authors.lastname: Ismaili
mesh_terms: D000953:Antigens, Protozoan / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000097:blood; D006801:Humans; D007231:Infant, Newborn / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D016778:Malaria, Falciparum / Q000276:immunology*; D010922:Placenta Diseases / Q000276:immunology* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016753:Interleukin-10; D007371:Interferon-gamma