Schistosoma mansoni egg antigens induce Treg that participate in diabetes prevention in NOD mice.
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.
Zaccone
Paola
P
Department of Pathology, University of Cambridge, Cambridge, UK.
Burton
Oliver
O
Miller
Nigel
N
Jones
Frances M
FM
Dunne
David W
DW
Cooke
Anne
A
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
D000947:Antigens, Helminth; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D037181:Lectins, C-Type; D016212:Transforming Growth Factor beta; D016753:Interleukin-10