Human γδT cells that inhibit the in vitro growth of the asexual blood stages of the Plasmodium falciparum parasite express cytolytic and proinflammatory molecules

The functional properties, regarding parasite growth inhibition in vitro, the cytotoxic potential and cytokine profiles of human γδ+ and αβ+ T cells, T-cell lines and clones stimulated with Plasmodium falciparum-antigen-or T-cell mitogen in vitro were investigated. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and specific primers, mRNA for the cytolytic molecules perforin, granzyme A and B, Fas and Fas ligand (FasL) were detected in both the γδ- and the αβT cells. Despite this fact, only γδT cells inhibited, both Vδ1+ and Vδ2+, the in vitro growth of the asexual blood stages in a dose dependent manner. The inhibition required cell-to-cell contact and was not observed until the second parasite replication implied that the likely γδT-cell target was the extracellular merozoite or schizont. The failure of αβT cells to inhibit the growth of the parasite suggests requirement of additional cytolytic molecules/signals or different receptor specificities exhibited by the γδT cells. Both the γδ- and αβT cells expressed mRNA for a large number of cytokines. Interferon (IFN)-γ, interleukin (IL) IL-5, IL-6, IL-8, tumour necrosis factor alpha (TNFα), tumour necrosis factor beta (TNF- β)/lymphotoxin (LT) and T-cell growth factor beta-1 (TGF-β1) were observed in all activated clones tested. No IL-3 was detected, while IL-1β, IL-2, IL- 4, IL-10 and GM-CSF were variably expressed. In conclusion, our data show that γδT cells in malaria nonimmune individuals inhibit the asexual blood stages of P. falciparum malaria, while similarly activated αβT cells do not. Thus, it is likely that the γδT cells could play a mandatory role in the elimination of parasites and/or the regulation of the early immune response to malaria infection.