Homeostatic regulation of T effector to Treg ratios in an area of seasonal malaria transmission

Finney, OC; Nwakanma, D; Conway, DJ; Walther, M; Riley, EM; (2009) Homeostatic regulation of T effector to Treg ratios in an area of seasonal malaria transmission. European journal of immunology, 39 (5). pp. 1288-1300. ISSN 0014-2980 DOI: https://doi.org/10.1002/eji.200839112

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An important aspect of clinical immunity to malaria is the ability to down-regulate inflammatory responses, once parasitaemia is under control, in order to avoid immune-mediated pathology. The role of classical (CD4(+)CD25(+)CD127(lo/-)FOXP3(+)) Treg in this process, however, remains controversial. Thus, we have characterized the frequency, phenotype and function of Treg populations, over time, in healthy individuals in The Gambia. We observed that both the percentage and the absolute number of CD4(+)FOXP3(+)CD127(lo/-) T cells were higher among individuals living in a rural village with highly seasonal malaria transmission than among individuals living in an urban area where malaria rarely occurs. These CD4(+)FOXP3(+)CD127(lo/-) T cells exhibited an effector memory and apoptosis-prone phenotype and suppressed cytokine production in response to malaria antigen. Cells from individuals exposed to malaria expressed significantly higher levels of mRNA for forkhead box P3 and T-box 21 (T-BET) at the end of the malaria transmission season than at the end of the non-transmission season. Importantly, the ratio of T-BET to forkhead box P3 was remarkably consistent between populations and over time, indicating that in healthy individuals, a transient increase in Th1 responses during the malaria transmission season is balanced by a commensurate Treg response, ensuring that immune homeostasis is maintained.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Malaria Centre
PubMed ID: 19338000
Web of Science ID: 266137700011
URI: http://researchonline.lshtm.ac.uk/id/eprint/5295


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