[PDF][PDF] Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction

Q Tang, JY Adams, C Penaranda, K Melli, E Piaggio… - Immunity, 2008 - cell.com
Q Tang, JY Adams, C Penaranda, K Melli, E Piaggio, E Sgouroudis, CA Piccirillo
Immunity, 2008cell.com
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 …
Summary
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.
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