Age-dependency of Plasmodium falciparum-specific and non-specific T cell cytokine responses in individuals from a malaria-endemic area

In areas where Plasmodium falciparum malaria is highly endemic, naturally acquired immunity develops slowly with increasing age. The mechanisms that lead to this protective immunity against P. falciparum are under intense investigation, as they might serve as models for the development of an efficient vaccine. In this study, we aimed to investigate the potential contribution of cell-mediated immune responses to the build-up of anti-malarial immunity by comparing the phenotypes and frequencies of both P. falciparum-specific and non-specific, cytokine-expressing T cells in a cross-sectional study of healthy children and adults, living in a malaria-endemic area in Central Africa. An increased capacity of CD3+ cells to produce interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, and of the TCRgammadelta+ subset to produce TNF-alpha was seen in adults after stimulation of peripheral blood mononuclear cells (PBMC) with a late-stage, schizont-rich, parasite preparation. Mitogenic stimulation with PMA and ionomycin induced much higher frequencies of IFN-gamma- and TNF-alpha-expressing CD4+, CD8+ as well as TCRgammadelta+ cells in adults, while differences for interleukin (IL)-2 expression were restricted to CD4+ and CD8+ T cells. For IL-10, neither specific nor non-specific stimulations of PBMC were associated with significant age-dependent alterations. Impressive increases in the capacity to produce P. falciparum-specific and non-specific IFN-gamma and TNF-alpha appear to be the main cellular correlates of naturally acquired immunity in Central Africa.