Human TcRγδ+ lymphocyte response on primary exposure to Plasmodium falciparum

In 29 patients experiencing their first P. falciparum malarial attack, blood levels of TcRγδ+ lymphocytes were studied from the onset of infection to up to 6-9 months later. Blood TcRγδ+ lymphocytes, revealed using the TcRδ1 monoclonal antibody (MoAb), were increased both in absolute and relative numbers. Alterations lasted for up to 3-4 months following the attack. A TiγA/BB3 reactive Vγ9 subset was preferentially amplified. In vitro, TcRγδ+ lymphocytes from both malaria-sensitized and unprimed donors responded to P. falciparum schizont extract (PFSE). PFSE-stimulated polyclonal T cell lines consisted principally in TcRγδ+ cells with a TiγA+/BB3+ phenotype. Several TcRγδ+ T cell clones obtained from patients recovering from acute malarial attack were maintained in the presence of PFSE and autologous irradiated PBL. They belong to the Vγ9 subset. In long-term cultures, TcRγδ+ clones progressively lost their capacity to react to PFSE antigen while they were able to proliferate and to exert cytotoxic activity in response to autologous TcRαβ+, PFSE-specific T lymphocyte clones. This suggests that regulatory interactions occur between activated TcRγδ+ and TcRαβ+ cells generated by P. falciparum. Sequential variations in blood TcRγδ+ and TcRαβ+ lymphocyte levels after primary exposure to P. falciparum suggest that such regulatory interactions may occur in vivo.