Constitutive activation and accelerated maturation of peripheral blood t cells in healthy adults in burkina faso compared to Germany: The case of malaria?

OBJECTIVE: It is not exactly known how frequent exposure to Plasmodium falciparum shapes the peripheral blood T-cell population in healthy West Africans. METHODS: The frequency of peripheral blood CD4(+ )lymphocytes responding to Plasmodium falciparum merozoite surface protein 1 (PfMSP-1) by production of interferon-gamma (IFN-γ), interleukin-2 (IL-2) or tumor necrosis factor-alpha (TNF-α) was determined using a commercially available flow cytometric activation assay (Fastlmmune) in 17 healthy adults in Nouna, Burkina Faso. T-cell activation and maturation in peripheral blood of healthy adults in Burkina Faso (n = 40) and Germany (n = 20) were compared using immunophenotyping and three-colour flow cytometry. RESULTS: Significant numbers of PfMSV-1 -specific CD4(+ )lymphocytes producing IFN-γ, IL-2 and/or TNF-α were detected in 14 healthy adults in Nouna. Cytokine profiles showed predominant production of IFN-γ and TNF-α. Compared to Germans, Burkinabé showed markedly lower proportions of CCR7(+ )CD45RA(+ )naïve CD4(+ )cells and slightly higher frequencies of CD95(+ )CD4(+ )T-cells and of CD38(+ )CD8(+ )T-cells. The median antibody-binding capacity of CD95(dim )CD4(+ )T-cells in Burkinabé was more than twice the value observed in Germans (263 vs. 108 binding sites per cell, p < 0.0001). CONCLUSIONS: We hypothesize that an IFN-γ-induced increase in the expression level of CD95 on CD4(+ )lymphocytes may lower the activation threshold of resting naïve CD4(+ )T-cells in healthy adults living in Burkina Faso. Bystander activation of these cells deserves further study as a molecular mechanism linking strong IFN-γ responses against Plasmodium falciparum to decreased susceptibility to parasitemia observed in specific ethnic groups in West Africa.