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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.

Type

Journal article

Journal

J Immunol

Publication Date

15/10/2001

Volume

167

Pages

4729 - 4737

Keywords

Adult, Amino Acid Sequence, Animals, Antigens, Protozoan, Epitopes, Gambia, Humans, Immunity, Cellular, Immunodominant Epitopes, Immunologic Memory, Interferon-gamma, Lymphocyte Activation, Malaria, Falciparum, Male, Molecular Sequence Data, Peptide Fragments, Plasmodium falciparum, Protozoan Proteins, T-Lymphocyte Subsets, T-Lymphocytes