Promoter haplotypes of the interleukin-10 gene influence proliferation of peripheral blood cells in response to helminth antigen.
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.
Timmann
C
C
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. timmann@bni.uni-hamburg.de
Fuchs
S
S
Thoma
C
C
Lepping
B
B
Brattig
N W
NW
Sievertsen
J
J
Thye
T
T
Müller-Myhsok
B
B
Horstmann
R D
RD
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
D000947:Antigens, Helminth; D016753:Interleukin-10