TGF-beta1 alters APC preference, polarizing islet antigen responses toward a Th2 phenotype.
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.
King
C
C
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Davies
J
J
Mueller
R
R
Lee
M S
MS
Krahl
T
T
Yeung
B
B
O'Connor
E
E
Sarvetnick
N
N
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects*; D001324:Autoantigens / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000276:immunology; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010641:Phenotype; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology*
D001324:Autoantigens; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D005968:Glutamate Decarboxylase