A proinsulin 74-90-derived protease-resistant, altered peptide ligand increases TGF-beta 1 secretion in PBMC from patients with type 1 diabetes mellitus

Denise van Aalst, Hubert Kalbacher, David Palesch, Fang Zou, Andreas Spyrantis, Silke Rosinger, Bernhard O Boehm, Timo Burster

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Proinsulin is a major diabetes-associated autoantigen. APL have been shown to manipulate the immune response of T cells. Here, we generated a lysosomal protease-resistant proinsulin 74-90-derived APL using a CS-directed amino acid modification approach. These prAPL activated TGF-beta 1 secretion in proinsulin-reactive T cells from PBMC of patients with T1D. We provide evidence that proinsulin-derived prAPL modulate the cytokine signature of proinsulin-reactive T cells at a micromolar range by increasing anti-inflammatory cytokines, including TGF-beta 1. Thus, the use of prAPL is a promising tool to mitigate autoaggressive T cells.

Original languageEnglish
Pages (from-to)943-8
Number of pages6
JournalJournal of Leukocyte Biology
Volume87
Issue number5
DOIs
Publication statusPublished - May 2010

Keywords

  • Amino Acid Sequence
  • Autoantigens
  • Cell Separation
  • Diabetes Mellitus, Type 1
  • Flow Cytometry
  • Humans
  • Leukocytes, Mononuclear
  • Ligands
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Proinsulin
  • T-Lymphocytes
  • Transforming Growth Factor beta1
  • Journal Article
  • Research Support, Non-U.S. Gov't

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