title: Promoter haplotypes of the interleukin-10 gene influence proliferation of peripheral blood cells in response to helminth antigen.
abstract: Since interleukin (IL)-10 is a key mediator of immunosuppression, and immunosuppression is considered an important element of helminth infection, we studied variants of the putative IL-10 gene promoter in 337 individuals from 130 families heavily exposed to infection by the tissue nematode Onchocerca volvulus. As shown by transmission disequilibrium tests, variants of the IL-10 promoter at positions -1082(G/A), -819(C/T), and -592(C/A) in the haplotype of ATA were significantly associated with high peripheral blood cell (PBC) proliferative responses to O. volvulus antigen (OvAg). No associations were observed using phytohemagglutinin-induced PBC proliferation or with qualitative or quantitative phenotypes of onchocerciasis or onchocerciasis-related skin disease. The findings are compatible with the hypothesis that the ATA haplotype causes a decrease in IL-10 production by OvAg-reactive type-1 regulatory T-lymphocytes, thereby alleviating the suppression of other T cells. To our knowledge, this is the first time that an influence of IL-10 promoter variants is shown on the adaptive immune response.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. timmann@bni.uni-hamburg.de
authors.forename: C
authors.initials: C
authors.lastname: Timmann
authors.forename: S
authors.initials: S
authors.lastname: Fuchs
authors.forename: C
authors.initials: C
authors.lastname: Thoma
authors.forename: B
authors.initials: B
authors.lastname: Lepping
authors.forename: N W
authors.initials: NW
authors.lastname: Brattig
authors.forename: J
authors.initials: J
authors.lastname: Sievertsen
authors.forename: T
authors.initials: T
authors.lastname: Thye
authors.forename: B
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: R D
authors.initials: RD
authors.lastname: Horstmann
mesh_terms: D000947:Antigens, Helminth / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D000947:Antigens, Helminth; D016753:Interleukin-10