Abstract
Immunization with Schistosoma mansoni soluble antigen preparations protects non-obese diabetic (NOD) mice against the development of type 1 diabetes. These preparations have long been known to induce Th2 responses in vitro and in vivo. Recently, two separate groups have reported that ω-1, a well-characterized glycoprotein in S. mansoni soluble egg antigens (SEA), which with IL-4 inducing principle of S. mansoni eggs (IPSE/α-1) is one of the two major glycoproteins secreted by live eggs, is a major SEA component responsible for this effect. We found that ω-1 induces Foxp3 as well as IL-4 expression when injected in vivo. We confirmed that ω-1 conditions DCs to drive Th2 responses and further demonstrated that ω-1 induces Foxp3(+) T cells from NOD mouse naïve T cells. In contrast, IPSE/α-1 did not drive Foxp3 responses. The in vitro development of Foxp3-expressing T cells by ω-1 was TGF-β- and retinoic acid-dependent. Our work, therefore, identifies ω-1 as an important factor for the induction of Foxp3(+) T cells by SEA in NOD mice.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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CD4-Positive T-Lymphocytes / pathology
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Cell Differentiation / drug effects
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Cells, Cultured
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dendritic Cells / pathology
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Diabetes Mellitus, Type 1 / immunology*
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Diabetes Mellitus, Type 1 / prevention & control
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Egg Proteins / administration & dosage
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / immunology
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Forkhead Transcription Factors / metabolism*
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Helminth Proteins / administration & dosage
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Immunization
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Interleukin-4 / genetics
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Interleukin-4 / immunology
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Interleukin-4 / metabolism*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred NOD
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Schistosoma mansoni / immunology*
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Schistosoma mansoni / metabolism
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Th2 Cells / immunology
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism
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Tretinoin / metabolism
Substances
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Egg Proteins
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Helminth Proteins
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IPSE protein, Schistosoma mansoni
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Transforming Growth Factor beta
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Interleukin-4
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Tretinoin