Distinct Roles for FOXP3+ and FOXP3− CD4+ T Cells in Regulating Cellular Immunity to Uncomplicated and Severe Plasmodium falciparum Malaria

PLoS Pathogens

Madi Njie¹  David J. Conway¹  Alfred Ngwa-Amambua²  David Jeffries³  Ian H. Cheeseman³  Joseph Okebe³  Emma Lawrence³  Eleanor M. Riley³  Shamanthi Jayasooriya³  Michael Walther³  Olivia C. Finney³  Augustine Ebonyi³  Natalia Gomez-Escobar³  Susanne Deininger³ 

[1] Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom;Institute of Medical Microbiology, Immunology and Parasitology, University Clinic Bonn, Bonn, Germany;Medical Research Council Laboratories, Fajara, Banjul, The Gambia

关键词: Malaria;    Regulatory T cells;    Parasitic diseases;    Malarial parasites;    T cells;    Immune response;    Cytokines;    Plasmodium;   

DOI  :  10.1371/journal.ppat.1000364

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to pathogenesis of severe malaria. To determine whether this balance is maintained by classical regulatory T cells (CD4+ FOXP3+ CD127−/low; Tregs) we compared cellular responses between Gambian children (n = 124) with severe Plasmodium falciparum malaria or uncomplicated malaria infections. Although no significant differences in Treg numbers or function were observed between the groups, Treg activity during acute disease was inversely correlated with malaria-specific memory responses detectable 28 days later. Thus, while Tregs may not regulate acute malarial inflammation, they may limit memory responses to levels that subsequently facilitate parasite clearance without causing immunopathology. Importantly, we identified a population of FOXP3−, CD45RO+ CD4+ T cells which coproduce IL-10 and IFN-γ. These cells are more prevalent in children with uncomplicated malaria than in those with severe disease, suggesting that they may be the regulators of acute malarial inflammation.

【 授权许可】

CC BY