Title | Effector Phenotype of Plasmodium falciparum-Specific CD4+ T Cells Is Influenced by Both Age and Transmission Intensity in Naturally Exposed Populations. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Boyle, MJ, Jagannathan, P, Bowen, K, McIntyre, TI, Vance, HM, Farrington, LA, Greenhouse, B, Nankya, F, Rek, J, Katureebe, A, Arinaitwe, E, Dorsey, G, Kamya, MR, Feeney, ME |
Journal | J Infect Dis |
Volume | 212 |
Issue | 3 |
Pagination | 416-25 |
Date Published | 2015 Aug 1 |
ISSN | 1537-6613 |
Keywords | Adult, CD4-Positive T-Lymphocytes, Child, Child, Preschool, Endemic Diseases, Female, Humans, Interferon-gamma, Interleukin-10, Longitudinal Studies, Malaria, Falciparum, Male, Middle Aged, Phenotype, Plasmodium falciparum, Uganda |
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. |
DOI | 10.1093/infdis/jiv054 |
Alternate Journal | J. Infect. Dis. |
PubMed ID | 25646355 |
PubMed Central ID | PMC4539911 |
Grant List | K23 AI100949 / AI / NIAID NIH HHS / United States K23AI100949 / AI / NIAID NIH HHS / United States K24 AI113002 / AI / NIAID NIH HHS / United States K24AI113002 / AI / NIAID NIH HHS / United States P30AI027763 / AI / NIAID NIH HHS / United States R01 AI093615 / AI / NIAID NIH HHS / United States R01AI093615 / AI / NIAID NIH HHS / United States U19 AI089674 / AI / NIAID NIH HHS / United States U19AI089674 / AI / NIAID NIH HHS / United States |