Gammadelta+ T cells preferentially respond to live rather than killed malaria parasites

Abstract

We have compared the in vitro responses of peripheral blood T cells from malaria-unexposed donors to live Plasmodium falciparum schizonts, freeze-thawed schizont extracts (P. falciparum schizont extracts [PfSE]), and parasite culture supernatants. We show that the cells responding to PfSE and parasite culture supernatants are predominantly CD4+ TCR alphabeta+ while in the presence of live schizonts there is an additional activation of TCR gammadelta+ cells. Activation of TCR gammadelta+ cells in response to PfSE was seen only when irradiated autologous feeder cells or recombinant interleukin-2 (IL-2) was added to the cultures. Live schizonts but not PfSE induced significant IL-2 production in vitro in the first 5 days after stimulation, suggesting that induction of early IL-2 by live parasites may contribute to the marked activation of the TCR gammadelta+ population.

FIG. 1

Lymphoproliferative responses of naive human PBMC to P. falciparum. Each symbol represents data from a single donor (7-day cultures). Cells from all donors proliferated in response to PHA, showing that they were viable (data not shown).

FIG. 2

Fluorescence-activated cell sorting plots showing proportions of TCRαβ⁺ and TCRγδ⁺ CD45RO⁺ lymphoblasts in cultures stimulated for 7 days with PfSE, live schizonts, or parasite culture supernatant for a single, representative donor. Only blasting cells were included in the gate. The numbers in each quadrant are the percentage of gated cells in that quadrant.

FIG. 3

IL-2 in culture supernatants of cells stimulated with PfSE (•) or live schizonts (○). Control cultures (stimulated with uRBC) all contained <20 pg of IL-2 per ml at each time point. PHA-stimulated cultures all contained >650 pg of IL-2 per ml after 24 h of stimulation.