Activation of γδ T Cells in Malaria: Interaction of Cytokines and a Schizont-Associated Plasmodium falciparum Antigen

A soluble Plasmodium falciparum antigen that specifically stimulates γδ T cells has been found associated predominantly with schizonts rather than ring forms, trophozoites, or gametocytes. This schizont-associated antigen (SAA) is resistant to protease digestion, is anionic at pH 8.5, is heat- and pH-resistant, and contains a phosphate group(s) that is crucial for biologic activity. Partially purified SAA induced proliferative responses and interferon-γ production by γδ T cells. These stimulatory effects were greatly enhanced by monocyte-derived cytokines, interleukin (IL)-10, IL-12, and IL-1β, but not by tumor necrosis factor-α. Taken together, these results suggest that concurrent stimulation of αδ T cells by SAA and by cytokines released from activated monocytes (IL-10, IL-12, IL-1β) may represent the major mechanism underlying the selective activation of γδ T cells that is consistently observed in clinical cases of P. falciparum infection.