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*
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford, United Kingdom;
Malaria Laboratory, Medical Research Council Laboratories, Fajara, The Gambia, West Africa; and
Vaccine and Infectious Diseases Unit, Austin Research Institute, Austin and Repatriation Medical Center, Heidelberg, Melbourne, Victoria, Australia
Natural immunity to malaria is characterized by low level CD4 T
cell reactivity detected by either lymphoproliferation or IFN-
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- secretion (ex vivo ELISPOT), IFN-
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- responses. This suggested
that the proliferating population, but not the IFN--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.
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