TGF-β1 alters APC preference, polarizing islet antigen responses toward a Th2 phenotype

Cecile King, Joanna Davies, Regula Mueller, Myung Shik Lee, Troy Krahl, Brian Yeung, Eric O'Connor, Nora Sarvetnick

Research output: Contribution to journalArticlepeer-review

169 Scopus citations

Abstract

TGF-β1, expressed in the pancreatic islets, protects the nonobese diabetic (NOD) mouse from insulin-independent diabetes mellitus (IDDM). The islet antigen-specific T cell response of ins-TGF-β1 mice relied on different antigen-presenting cells (APC) from those used by NOD T cells. T cells from NOD mice utilized B cells to present islet antigen, whereas T cells from ins-TGF-β1 mice utilized macrophages. In addition, the islet antigen-specific T cell repertoire of ins-TGFβ1 mice was distinct and deviated toward an IL-4-producing Th2 phenotype. When ins-TGF-β1 mice were treated with anti-IL-4 antibody, islet antigen-specific IFN-γ-producing Th1 cells were unleashed, and the incidence of diabetes increased to the level of NOD mice. This suggests active suppression of a diabetogenic T cell response. This study describes a novel mechanism in which expression of TGF-β1 in the context of self-antigen shifts APC preference, deviating T cell responses to a Th2 phenotype, preventing IDDM.

Original languageEnglish (US)
Pages (from-to)601-613
Number of pages13
JournalImmunity
Volume8
Issue number5
DOIs
StatePublished - May 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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