Central Role of Defective Interleukin-2 Production in the Triggering of Islet Autoimmune Destruction

Qizhi Tang, Jason Yeates Adams, Cristina Penaranda, Kristin Melli, Eliane Piaggio, Evridiki Sgouroudis, Ciriaco A. Piccirillo, Benoit L. Salomon, Jeffrey A. Bluestone

Research output: Contribution to journalArticle

501 Scopus citations

Abstract

The dynamics of CD4+ effector T cells (Teff cells) and CD4+Foxp3+ regulatory T cells (Treg cells) during diabetes progression in nonobese diabetic mice was investigated to determine whether an imbalance of Treg cells and Teff cells contributes to the development of type 1 diabetes. Our results demonstrated a progressive decrease in the Treg cell:Teff cell ratio in inflamed islets but not in pancreatic lymph nodes. Intra-islet Treg cells expressed reduced amounts of CD25 and Bcl-2, suggesting that their decline was due to increased apoptosis. Additionally, administration of low-dose interleukin-2 (IL-2) promoted Treg cell survival and protected mice from developing diabetes. Together, these results suggest intra-islet Treg cell dysfunction secondary to defective IL-2 production is a root cause of the progressive breakdown of self-tolerance and the development of diabetes in nonobese diabetic mice.

Original languageEnglish (US)
Pages (from-to)687-697
Number of pages11
JournalImmunity
Volume28
Issue number5
DOIs
StatePublished - May 16 2008

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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    Tang, Q., Adams, J. Y., Penaranda, C., Melli, K., Piaggio, E., Sgouroudis, E., Piccirillo, C. A., Salomon, B. L., & Bluestone, J. A. (2008). Central Role of Defective Interleukin-2 Production in the Triggering of Islet Autoimmune Destruction. Immunity, 28(5), 687-697. https://doi.org/10.1016/j.immuni.2008.03.016