TGF-beta1 alters APC preference, polarizing islet antigen responses toward a Th2 phenotype

Immunity. 1998 May;8(5):601-13. doi: 10.1016/s1074-7613(00)80565-8.


TGF-beta1, expressed in the pancreatic islets, protects the nonobese diabetic (NOD) mouse from insulin-dependent diabetes mellitus (IDDM). The islet antigen-specific T cell response of ins-TGF-beta1 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-beta1 mice utilized macrophages. In addition, the islet antigen-specific T cell repertoire of ins-TGF-beta1 mice was distinct and deviated toward an IL-4-producing Th2 phenotype. When ins-TGF-beta1 mice were treated with anti-iL-4 antibody, islet antigen-specific IFNGamma-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-beta1 in the context of self-antigen shifts APC preference, deviating T cell responses to a Th2 phenotype, preventing IDDM.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / drug effects*
  • Autoantigens / immunology*
  • Diabetes Mellitus, Type 1 / immunology
  • Glutamate Decarboxylase / immunology
  • Immune Tolerance
  • Interleukin-4 / immunology
  • Islets of Langerhans / immunology*
  • Mice
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Phenotype
  • Spleen / immunology
  • Spleen / metabolism
  • Th2 Cells / immunology*
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / immunology*


  • Autoantigens
  • Transforming Growth Factor beta
  • Interleukin-4
  • Glutamate Decarboxylase