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Distinct Roles for FOXP3+ and FOXP32 CD4+ T Cells in Regulating Cellular Immunity to Uncomplicated and Severe Plasmodium falciparum Malaria 1 1 1,2 1 1 Michael Walther *, David Jeffries , Olivia C. Finney , Madi Njie , Augustine Ebonyi , Susanne 1,3 1 1 1 1,2 Deininger , Emma Lawrence , Alfred Ngwa-Amambua , Shamanthi Jayasooriya , Ian H. Cheeseman , 1 1 1,2 2 Natalia Gomez-Escobar , Joseph Okebe , David J. Conway , Eleanor M. Riley 1 Medical Research Council Laboratories, Fajara, Banjul, The Gambia, 2 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom, 3 Institute of Medical Microbiology, Immunology and Parasitology, University Clinic Bonn, Bonn, Germany Abstract 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+ CD1272/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