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

Autor:	Boyle MJ; Department of Medicine Center for Biomedical Research, Burnet Institute, Melbourne, Australia., Jagannathan P; Department of Medicine., Bowen K; Department of Medicine., McIntyre TI; Department of Medicine., Vance HM; Department of Medicine., Farrington LA; Department of Medicine., Greenhouse B; Department of Medicine., Nankya F; Infectious Diseases Research Collaboration., Rek J; Infectious Diseases Research Collaboration., Katureebe A; Infectious Diseases Research Collaboration., Arinaitwe E; Infectious Diseases Research Collaboration., Dorsey G; Department of Medicine., Kamya MR; Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda., Feeney ME; Department of Medicine Department of Pediatrics, University of California-San Francisco.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2015 Aug 01; Vol. 212 (3), pp. 416-25. Date of Electronic Publication: 2015 Feb 02.
DOI:	10.1093/infdis/jiv054
Abstrakt:	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. (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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