Effector Phenotype of Plasmodium falciparum-Specific CD4+ T Cells Is Influenced by Both Age and Transmission Intensity in Naturally Exposed Populations

J Infect Dis. 2015 Aug 1;212(3):416-25. doi: 10.1093/infdis/jiv054. Epub 2015 Feb 2.


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.

Keywords: CD4+ T cells; IFN-γ; IL-10; P. falciparum; cellular immunity; malaria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • Child
  • Child, Preschool
  • Endemic Diseases
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Longitudinal Studies
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / parasitology
  • Malaria, Falciparum / transmission
  • Male
  • Middle Aged
  • Phenotype
  • Plasmodium falciparum / immunology*
  • Uganda / epidemiology


  • Interleukin-10
  • Interferon-gamma