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 journalArticle

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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

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Antigen-Presenting Cells
T-Lymphocytes
Phenotype
Antigens
Inbred NOD Mouse
Interleukin-4
Diabetes Mellitus
Th1 Cells
Autoantigens
Islets of Langerhans
B-Lymphocytes
Macrophages
Insulin
Antibodies
Incidence
Mouse Ins1 protein

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

TGF-β1 alters APC preference, polarizing islet antigen responses toward a Th2 phenotype. / King, Cecile; Davies, Joanna; Mueller, Regula; Lee, Myung Shik; Krahl, Troy; Yeung, Brian; O'Connor, Eric; Sarvetnick, Nora.

In: Immunity, Vol. 8, No. 5, 05.1998, p. 601-613.

Research output: Contribution to journalArticle

King, C, Davies, J, Mueller, R, Lee, MS, Krahl, T, Yeung, B, O'Connor, E & Sarvetnick, N 1998, 'TGF-β1 alters APC preference, polarizing islet antigen responses toward a Th2 phenotype', Immunity, vol. 8, no. 5, pp. 601-613. https://doi.org/10.1016/S1074-7613(00)80565-8
King, Cecile ; Davies, Joanna ; Mueller, Regula ; Lee, Myung Shik ; Krahl, Troy ; Yeung, Brian ; O'Connor, Eric ; Sarvetnick, Nora. / TGF-β1 alters APC preference, polarizing islet antigen responses toward a Th2 phenotype. In: Immunity. 1998 ; Vol. 8, No. 5. pp. 601-613.
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