title: Schistosoma mansoni egg antigens induce Treg that participate in diabetes prevention in NOD mice.
abstract: Schistosoma mansoni soluble egg antigens (SEA) profoundly regulate the infected host's immune system. We previously showed that SEA prevents type 1 diabetes in NOD mice and that splenocytes from SEA-treated mice have reduced ability to transfer diabetes to NOD.scid recipients. To further characterize the mechanism of diabetes prevention we examined the cell types involved and showed that CD25(+) T-cell depletion of splenocytes from SEA-treated donors restored their ability to transfer diabetes. Furthermore, SEA treatment increased the number and proportional representation of Foxp3(+) T cells in the pancreas of NOD mice. We have used in vitro systems to analyze the effect of SEA on the development of NOD Foxp3(+) T cells. We find that SEA can induce Foxp3 expression in naïve T cells in a TGF-beta-dependent manner. Foxp3 induction requires the presence of DC, which we also show are modified by SEA to upregulate C-type lectins, IL-10 and IL-2. Our studies show that SEA can have a direct effect on CD4(+) T cells increasing expression of TGF-beta, integrin beta8 and galectins. These effects of SEA on DC and T cells may act in synergy to induce Foxp3(+) Treg in the NOD mouse.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: Paola
authors.initials: P
authors.lastname: Zaccone
authors.forename: Oliver
authors.initials: O
authors.lastname: Burton
authors.forename: Nigel
authors.initials: N
authors.lastname: Miller
authors.forename: Frances M
authors.initials: FM
authors.lastname: Jones
authors.forename: David W
authors.initials: DW
authors.lastname: Dunne
authors.forename: Anne
authors.initials: A
authors.lastname: Cooke
mesh_terms: D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D010063:Ovum / Q000276:immunology*; D010179:Pancreas / Q000187:drug effects / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: D000947:Antigens, Helminth; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D037181:Lectins, C-Type; D016212:Transforming Growth Factor beta; D016753:Interleukin-10