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 gamma delta(+) and alpha beta(+) 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 gamma delta- and the alpha beta T cells. Despite this fact, only gamma delta T cells inhibited, both V delta 1(+) and V delta 2(+), 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 gamma delta T-cell target was the extracellular merozoite or schizont. The failure of alpha beta T cells to inhibit the growth of the parasite suggests requirement of additional cytolytic molecules/signals or different receptor specificities exhibited by the gamma delta T cells. Both the gamma delta- and alpha beta T cells expressed mRNA for a large number of cytokines. Interferon (IFN)-gamma, interleukin (IL) IL-5, IL-6, IL-8, tumour necrosis factor alpha (TNF alpha), tumour necrosis factor beta (TNF-beta)/lymphotoxin (LT) and T-cell growth factor beta-1 (TGF-beta 1) were observed in all activated clones tested. No IL-3 was detected, while IL-1 beta, IL-2, IL-4, IL-10 and GM-CSF were variably expressed. In conclusion, our data show that gamma delta T cells in malaria nonimmune individuals inhibit the asexual blood stages of P. falciparum malaria, while similarly activated alpha beta T cells do not. Thus, it is likely that the gamma delta T cells could play a mandatory role in the elimination of parasites and/or the regulation of the early immune response to malaria infection.