The S. mansoni glycoprotein ω-1 induces Foxp3 expression in NOD mouse CD4⁺ T cells

Eur J Immunol. 2011 Sep;41(9):2709-18. doi: 10.1002/eji.201141429. Epub 2011 Aug 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / prevention & control
  • Egg Proteins / administration & dosage
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism*
  • Helminth Proteins / administration & dosage
  • Immunization
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Schistosoma mansoni / immunology*
  • Schistosoma mansoni / metabolism
  • Th2 Cells / immunology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Tretinoin / metabolism

Substances

  • Egg Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Helminth Proteins
  • IPSE protein, Schistosoma mansoni
  • Transforming Growth Factor beta
  • Interleukin-4
  • Tretinoin