title: Interleukin 10 (IL-10)-producing CD1dhi regulatory B cells from Schistosoma haematobium-infected individuals induce IL-10-positive T cells and suppress effector T-cell cytokines.
abstract: BACKGROUND
  Chronic schistosome infections are associated with T-cell hyporesponsiveness and a strong regulatory network. Murine studies have shown that schistosome infections can induce regulatory CD1d(hi) B cells, which inhibit inflammatory responses. Here, we evaluated the influence of regulatory B cells (Bregs) on T-cell cytokines in vitro in human schistosomiasis.
  
  
  METHODS
  Gabonese young adults were recruited from areas where Schistosoma haematobium (S.h) infections were high or low endemic. The study participants were categorized as infected or uninfected from an high endemic area or uninfected from a low endemic (nonendemic) area. Their B cells were studied for Breg subset markers and cocultured with allogenic anti-CD3-stimulated CD4(+) T cells, followed by T-cell cytokine analysis.
  
  
  RESULTS
  A greater percentage of B cells from S. haematobium-infected donors expressed cytoplasmic interleukin 10 (IL-10) and membrane-bound latency-associated peptide/transforming growth factor β1, compared with uninfected donors. T cells produced less interferon γ, interleukin 4, and interleukin 17 upon coculture with B cells from schistosome-infected individuals only, while the conversion to CD25(hi)FoxP3(+) and the percentage of IL-10(+) T cells was enhanced. Interestingly, depletion of the prominent IL-10-producing B-cell subset, CD1d(hi) cells, resulted in less IL-10(+) T cells in the S. haematobium-infected group, while levels of FoxP3(+) regulatory T cells remained unaffected.
  
  
  CONCLUSIONS
  Schistosomes can induce functional Bregs in humans that may be instrumental in general T-cell hyporesponsiveness and may contribute to the increased regulatory milieu found in schistosomiasis.
authors.affiliation: Department of Parasitology, Leiden University Medical Center, the Netherlands.
authors.forename: Luciën E P M
authors.initials: LE
authors.lastname: van der Vlugt
authors.affiliation: Centre de Recherches Médicales de Lambaréné, Gabon.
authors.forename: Jeannot F
authors.initials: JF
authors.lastname: Zinsou
authors.affiliation: Department of Parasitology, Leiden University Medical Center, the Netherlands.
authors.forename: Arifa
authors.initials: A
authors.lastname: Ozir-Fazalalikhan
authors.affiliation: Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Germany.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.affiliation: Department of Parasitology, Leiden University Medical Center, the Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Yazdanbakhsh
authors.affiliation: Centre de Recherches Médicales de Lambaréné, Gabon Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Germany.
authors.forename: Ayola A
authors.initials: AA
authors.lastname: Adegnika
authors.affiliation: Department of Parasitology, Leiden University Medical Center, the Netherlands.
authors.forename: Hermelijn H
authors.initials: HH
authors.lastname: Smits
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism*; D060151:B-Lymphocytes, Regulatory / Q000378:metabolism*; D016207:Cytokines / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D005681:Gabon / Q000453:epidemiology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D012548:Schistosoma haematobium; D012553:Schistosomiasis haematobia / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D018949:Antigens, CD1; D016207:Cytokines; D016753:Interleukin-10
keywords: IL-10; TGF-β; Tr1; Treg cell; human; regulatory B cell; schistosomiasis