gd T cells inhibit the in vitro growth of the asexual blood stage of Plasmodium falciparum by a granule exocytosis-dependent cytotoxic pathway that requires granulysin

Abstract

Several reports have stated the ability of gamma delta T cells to inhibit the growth of the asexual blood stages of Plasmodium falciparum in vitro. However, little information is available about the mechanisms involved. In this study, in vitro systems were used to study the role of the granule exocytosis-dependent cytotoxic pathway in the growth inhibition/killing of P. falciparum by human gamma delta T cells. Our results show that the inhibition requires cell-to-cell contact and that gamma delta T cells kill the asexual blood stages of P. falciparum through a granule exocytosis-dependent cytotoxic pathway after recognition of certain ligands or molecules expressed on the surface of infected erythrocytes or merozoites. The in vitro inhibitory capacity of gamma delta T cells was strongly correlated with the expression of granulysin in the cytotoxic granules, while non-inhibitory CD4+ and CD8+ T cells expressed very little, implicating a role for granulysin in parasite inhibition. This was further suggested by the addition of neutralizing anti-granulysin antibodies, which abrogated the parasite inhibitory capacity of the gamma delta T cells. Taken together, our results suggest that the capacity of gamma delta T cells for inhibition/killing of P. falciparum is based on the granule exocytosis-dependent cytotoxic pathway and that the presence of granulysin is essential to maintain efficient killing.