Interactions of CD4+ and CD8+ human T lymphocytes from malaria-unprimed donors with Plasmodium falciparum schizont stage

Abstract

During Plasmodium falciparum malaria, a wide spectrum of parasite-encoded blood-stage proteins is presented to the immune system of the host. To explore their multiple interactions with T cells from donors who have had no previous exposure to the parasite, whole schizont extract was used in vitro. Both CD4+ and CD8+ lymphocytes from all individuals tested were stimulated to proliferate. The responses were dependent on the presence of accessory cells and were only partially replaced by recombinant interleukin-1. Responses were inhibited by monoclonal antibodies to CD3, the alpha beta-chain T-cell receptor, or CD4 molecules but not to CD2. P. falciparum schizont extract-specific T-cell clones were generated and maintained by using sole stimulation by P. falciparum extract with autologous accessory cells or recombinant interleukin-2. Monoclonal antibodies to CD3 (or the alpha beta-chain T-cell receptor) blocked cloned T-cell responses to the schizont extract, and although the responses of the majority of the CD4+ or CD8+ T-cell clones were restricted by autologous accessory cells and inhibited by monoclonal antibodies to either CD4 or CD8, other clones responded to P. falciparum in the absence of accessory cells and were not regulated by the same monoclonal antibodies. The last category of clones consisted of autoreactive T cells. These data suggest that at the first contact with P. falciparum, requirements are met for significant T-cell stimulation.