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

Cite this

Flanagan, K. L., Lee, E. A. M., Gravenor, M. B., Reece, W. H. H., Urban, B. C., Doherty, T., Bojang, K. A., Pinder, M., Hill, A. V. S., & Plebanski, M. (2001). Unique T cell effector functions elicited by Plasmodium falciparum epitopes in malaria-exposed Africans tested by three T cell assays. Journal of Immunology, 167(8), 4729-4737.