Protective Role of γδ T Lymphocytes during Plasmodium falciparum Infection

Abstract

Human T γδ lymphocytes, bearing Vγ9 Vδ2 chains, constitute a small proportion (1–5%) of the lymphocytes in the blood. These cells recognize nonpeptidic molecules such as phosphoantigens, intermediary metabolites products by microorganisms, including parasites. These antigens are recognized in the absence of molecules CMH. Our previous results have shown that Plasmodium falciparum synthetize phosphoantigen, intermediary products of the Rohmer pathway. These phosphoantigens are able to induce the proliferation of T γδ lymphocytes, producing pro‐inflammatory cytokines and providing a parasitotoxic activity against parasitized red blood cells. Also, during the acute phase of infection, these lymphocytes increase both in percentage and numbers. Today, the biological role of T γδ lymphocytes remains poorly understood. Indeed, these lymphocytes are found in primates but there is no equivalent in rodents. We decided to study this population in the infection model Plasmodium falciparum/spleen intact Saimiri scirieus. In this monkey, we found a population of TVγ9 (representing 0.2–1% of total lymphocytes in the peripheral blood) which react with phosphoantigens as do human TVγ9 cells. Activation kinetics of these cells in infected monkeys show an early activation occuring on the 6th day of infection, while the CD4 T activation starts at day 10. Also, we observed an important increase of numbers and percentages of these TVγ9. Their maximal peak coincides with the beginning of parasite clearance. Together, these data associated with parasitotoxic activity in vitro argue for a role of TVγ9 cells in parasitemia control, particulary during primary infection.