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

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

Author information

1
Department of Medicine Center for Biomedical Research, Burnet Institute, Melbourne, Australia.
2
Department of Medicine.
3
Infectious Diseases Research Collaboration.
4
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
5
Department of Medicine Department of Pediatrics, University of California-San Francisco.

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.

KEYWORDS:

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

PMID:
25646355
PMCID:
PMC4539911
DOI:
10.1093/infdis/jiv054
[Indexed for MEDLINE]
Free PMC Article

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