Decline of FoxP3+ Regulatory CD4 T Cells in Peripheral Blood of Children Heavily Exposed to Malaria.

TitleDecline of FoxP3+ Regulatory CD4 T Cells in Peripheral Blood of Children Heavily Exposed to Malaria.
Publication TypeJournal Article
Year of Publication2015
AuthorsBoyle, MJ, Jagannathan, P, Farrington, LA, Eccles-James, I, Wamala, S, McIntyre, TI, Vance, HM, Bowen, K, Nankya, F, Auma, A, Nalubega, M, Sikyomu, E, Naluwu, K, Rek, J, Katureebe, A, Bigira, V, Kapisi, J, Tappero, J, Muhindo, MK, Greenhouse, B, Arinaitwe, E, Dorsey, G, Kamya, MR, Feeney, ME
JournalPLoS Pathog
Volume11
Issue7
Paginatione1005041
Date Published2015 Jul
ISSN1553-7374
Abstract

FoxP3+ regulatory CD4 T cells (Tregs) help to maintain the delicate balance between pathogen-specific immunity and immune-mediated pathology. Prior studies suggest that Tregs are induced by P. falciparum both in vivo and in vitro; however, the factors influencing Treg homeostasis during acute and chronic infections, and their role in malaria immunopathogenesis, remain unclear. We assessed the frequency and phenotype of Tregs in well-characterized cohorts of children residing in a region of high malaria endemicity in Uganda. We found that both the frequency and absolute numbers of FoxP3+ Tregs in peripheral blood declined markedly with increasing prior malaria incidence. Longitudinal measurements confirmed that this decline occurred only among highly malaria-exposed children. The decline of Tregs from peripheral blood was accompanied by reduced in vitro induction of Tregs by parasite antigen and decreased expression of TNFR2 on Tregs among children who had intense prior exposure to malaria. While Treg frequencies were not associated with protection from malaria, there was a trend toward reduced risk of symptomatic malaria once infected with P. falciparum among children with lower Treg frequencies. These data demonstrate that chronic malaria exposure results in altered Treg homeostasis, which may impact the development of antimalarial immunity in naturally exposed populations.

DOI10.1371/journal.ppat.1005041
Alternate JournalPLoS Pathog.
PubMed ID26182204
PubMed Central IDPMC4504515
Grant ListK23 AI100949 / AI / NIAID NIH HHS / United States
K23 AI100949 / 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
U19AI089674 / AI / NIAID NIH HHS / United States
U62P024421 / / PHS HHS / United States