Unique T cell effector functions elicited by Plasmodium falciparum epitopes in malaria-exposed Africans tested by three T cell assays

K. L. Flanagan, E. A M Lee, M. B. Gravenor, W. H H Reece, B. C. Urban, T. Doherty, K. A. Bojang, M. Pinder, A. V S Hill, M. Plebanski

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Abstract

Natural immunity to malaria is characterized by low level CD4 T cell reactivity detected by either lymphoproliferation or IFN-γ 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-γ secretion (ex vivo ELISPOT), IFN-γ 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-γ responses. This suggested that the proliferating population, but not the IFN-γ-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.

Original languageEnglish
Pages (from-to)4729-4737
Number of pages9
JournalJournal of Immunology
Volume167
Issue number8
Publication statusPublished - 15 Oct 2001
Externally publishedYes

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