title: Unique T cell effector functions elicited by Plasmodium falciparum epitopes in malaria-exposed Africans tested by three T cell assays.
abstract: Natural immunity to malaria is characterized by low level CD4 T cell reactivity detected by either lymphoproliferation or IFN-gamma secretion. Here we show a doubling in the detection rate of responders to the carboxyl terminus of circumsporozoite protein (CS) of Plasmodium falciparum by employing three T cell assays simultaneously: rapid IFN-gamma secretion (ex vivo ELISPOT), IFN-gamma secretion after reactivation of memory T cells and expansion in vitro (cultured ELISPOT), and lymphoproliferation. Remarkably, for no individual peptide did a positive response for one T cell effector function correlate with any other. Thus these CS epitopes elicited unique T cell response patterns in malaria-exposed donors. Novel or important epitope responses may therefore be missed if only one T cell assay is employed. A borderline correlation was found between anti-CS Ab levels and proliferative responses, but no correlation was found with ex vivo or cultured IFN-gamma responses. This suggested that the proliferating population, but not the IFN-gamma-secreting cells, contained cells that provide help for Ab production. The data suggest that natural immunity to malaria is a complex function of T cell subgroups with different effector functions and has important implications for future studies of natural T cell immunity.
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom. katflan@hotmail.com
authors.forename: K L
authors.initials: KL
authors.lastname: Flanagan
authors.forename: E A
authors.initials: EA
authors.lastname: Lee
authors.forename: M B
authors.initials: MB
authors.lastname: Gravenor
authors.forename: W H
authors.initials: WH
authors.lastname: Reece
authors.forename: B C
authors.initials: BC
authors.lastname: Urban
authors.forename: T
authors.initials: T
authors.lastname: Doherty
authors.forename: K A
authors.initials: KA
authors.lastname: Bojang
authors.forename: M
authors.initials: M
authors.lastname: Pinder
authors.forename: A V
authors.initials: AV
authors.lastname: Hill
authors.forename: M
authors.initials: M
authors.lastname: Plebanski
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D000939:Epitopes; D005714:Gambia; D006801:Humans; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D000939:Epitopes; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma