title: Constitutive activation and accelerated maturation of peripheral blood T cells in healthy adults in Burkina Faso compared to Germany: the case of malaria?
abstract: 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 (FastImmune) 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 PfMSP-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+ naive 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 naive 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.
authors: Department of Infectious Diseases, Virology, University of Heidelberg, INF324, 69120 Heidelberg, Germany.
authors: F
authors: F
authors: Tiba
authors: F
authors: F
authors: Nauwelaers
authors: L
authors: L
authors: Sangare
authors: B
authors: B
authors: Coulibaly
authors: V
authors: V
authors: Mrosek
authors: Hans-Georg
authors: HG
authors: Kräusslich
authors: T
authors: T
authors: Böhler
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology / Q000378:metabolism; D000328:Adult; D002050:Burkina Faso; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005858:Germany; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D020066:Merozoite Surface Protein 1 / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology / Q000472:pathogenicity*; D054400:Receptors, CCR7 / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D055815:Young Adult; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: C515370:CCR7 protein, human; C491901:FAS protein, human; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D020066:Merozoite Surface Protein 1; D054400:Receptors, CCR7; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1