Efficacy of clonal deletion vs. anergy of self-reactive CD4 T-cells for the prevention and reversal of autoimmune diabetes

Anca Preda-Pais, Alexandru C. Stan, Sofia Casares, Constantin Bona, Teodor D. Brumeanu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The self-reactive CD4 T-cells play an essential role in triggering and sustaining organ-specific autoimmune diseases. Silencing or elimination of these cells can prevent and reverse an autoimmune process. We have previously showed that a single dose-administration of a soluble dimeric MHC II-peptide chimera (DEF) in double-transgenic mice delayed the onset autoimmune diabetes, and restored the euglycemia in already diabetic mice for a period of 1 week. DEF dimer protection relied on induction of anergy of diabetogenic CD4 T-cells in spleen, and stimulation of IL-10-secreting T regulatory type 1 cells in pancreas. Herein, we show that an octameric form of DEF has doubled the period of protection and reversal of disease by clonal deletion of diabetogenic CD4 T-cells in both the thymic and peripheral compartments. Deletion occurred by activation-induced cell death subsequent to repartitioning and signaling of FAS-FADD apoptotic module in the plasma membrane lipid rafts. Our previous and present data indicated first, that DEF valence translates into various effects on the antigen-specific CD4 T-cells, i.e., Th2 immune deviation, anergy, and apoptosis. Second, the present findings argue for a better efficacy of clonal deletion than anergy of diabetogenic CD4 T-cells for the protection and reversal of autoimmune diabetes.

Original languageEnglish
Pages (from-to)21-32
Number of pages12
JournalJournal of Autoimmunity
Volume25
Issue number1
DOIs
StatePublished - Aug 2005

Keywords

  • Autoimmune diabetes
  • CD4 T-cells
  • Clonal deletion
  • MHC II-peptide chimeras

Fingerprint

Dive into the research topics of 'Efficacy of clonal deletion vs. anergy of self-reactive CD4 T-cells for the prevention and reversal of autoimmune diabetes'. Together they form a unique fingerprint.

Cite this