title: Effector Phenotype of Plasmodium falciparum-Specific CD4+ T Cells Is Influenced by Both Age and Transmission Intensity in Naturally Exposed Populations.
abstract: BACKGROUND
  Mechanisms mediating immunity to malaria remain unclear, but animal data and experimental human vaccination models suggest a critical role for CD4(+) T cells. Advances in multiparametric flow cytometry have revealed that the functional quality of pathogen-specific CD4(+) T cells determines immune protection in many infectious models. Little is known about the functional characteristics of Plasmodium-specific CD4(+) T-cell responses in immune and nonimmune individuals.
  
  
  METHODS
  We compared T-cell responses to Plasmodium falciparum among household-matched children and adults residing in settings of high or low malaria transmission in Uganda. Peripheral blood mononuclear cells were stimulated with P. falciparum antigen, and interferon γ (IFN-γ), interleukin 2, interleukin 10, and tumor necrosis factor α (TNF-α) production was analyzed via multiparametric flow cytometry.
  
  
  RESULTS
  We found that the magnitude of the CD4(+) T-cell responses was greater in areas of high transmission but similar between children and adults in each setting type. In the high-transmission setting, most P. falciparum-specific CD4(+) T-cells in children produced interleukin 10, while responses in adults were dominated by IFN-γ and TNF-α. In contrast, in the low-transmission setting, responses in both children and adults were dominated by IFN-γ and TNF-α.
  
  
  CONCLUSIONS
  These findings highlight major differences in the CD4(+) T-cell response of immune adults and nonimmune children that may be relevant for immune protection from malaria.
authors: Department of Medicine Center for Biomedical Research, Burnet Institute, Melbourne, Australia.
authors: Michelle J
authors: MJ
authors: Boyle
authors: Department of Medicine.
authors: Prasanna
authors: P
authors: Jagannathan
authors: Department of Medicine.
authors: Katherine
authors: K
authors: Bowen
authors: Department of Medicine.
authors: Tara I
authors: TI
authors: McIntyre
authors: Department of Medicine.
authors: Hilary M
authors: HM
authors: Vance
authors: Department of Medicine.
authors: Lila A
authors: LA
authors: Farrington
authors: Department of Medicine.
authors: Bryan
authors: B
authors: Greenhouse
authors: Infectious Diseases Research Collaboration.
authors: Felistas
authors: F
authors: Nankya
authors: Infectious Diseases Research Collaboration.
authors: John
authors: J
authors: Rek
authors: Infectious Diseases Research Collaboration.
authors: Agaba
authors: A
authors: Katureebe
authors: Infectious Diseases Research Collaboration.
authors: Emmanuel
authors: E
authors: Arinaitwe
authors: Department of Medicine.
authors: Grant
authors: G
authors: Dorsey
authors: Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
authors: Moses R
authors: MR
authors: Kamya
authors: Department of Medicine Department of Pediatrics, University of California-San Francisco.
authors: Margaret E
authors: ME
authors: Feeney
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology / Q000635:transmission; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010963:Plasmodium falciparum / Q000276:immunology*; D014454:Uganda / Q000453:epidemiology
chemical_list: D016753:Interleukin-10; D007371:Interferon-gamma
keywords: CD4+ T cells; IFN-γ; IL-10; P. falciparum; cellular immunity; malaria
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