title: Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection.
abstract: Understanding the regulation of immune responses is central for control of autoimmune and infectious disease. In murine models of autoimmunity and chronic inflammatory disease, potent regulatory T lymphocytes have recently been characterized. Despite an explosion of interest in these cells, their relevance to human disease has been uncertain. In a longitudinal study of malaria sporozoite infection via the natural route, we provide evidence that regulatory T cells have modifying effects on blood-stage infection in vivo in humans. Cells with the characteristics of regulatory T cells are rapidly induced following blood-stage infection and are associated with a burst of TGF-beta production, decreased proinflammatory cytokine production, and decreased antigen-specific immune responses. Both the production of TGF-beta and the presence of CD4+CD25+FOXP3+ regulatory T cells are associated with higher rates of parasite growth in vivo. P. falciparum-mediated induction of regulatory T cells may represent a parasite-specific virulence factor.
authors.affiliation: Center for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Churchill Hospital, Oxford OX3 7LJ, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Walther
authors.forename: Jon Eric
authors.initials: JE
authors.lastname: Tongren
authors.forename: Laura
authors.initials: L
authors.lastname: Andrews
authors.forename: Daniel
authors.initials: D
authors.lastname: Korbel
authors.forename: Elizabeth
authors.initials: E
authors.lastname: King
authors.forename: Helen
authors.initials: H
authors.lastname: Fletcher
authors.forename: Rikke F
authors.initials: RF
authors.lastname: Andersen
authors.forename: Philip
authors.initials: P
authors.lastname: Bejon
authors.forename: Fiona
authors.initials: F
authors.lastname: Thompson
authors.forename: Susanna J
authors.initials: SJ
authors.lastname: Dunachie
authors.forename: Fanny
authors.initials: F
authors.lastname: Edele
authors.forename: J Brian
authors.initials: JB
authors.lastname: de Souza
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sinden
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Riley
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D002986:Clinical Trials as Topic; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D051858:Forkhead Transcription Factors; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D016212:Transforming Growth Factor beta / Q000097:blood / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D015704:CD4 Antigens; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta