Endogenous expansion of regulatory T cells leads to long-term islet graft survival in diabetic NOD mice

Q. Shi, J. R. Lees, D. W. Scott, D. L. Farber, S. T. Bartlett*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Donor pancreatic lymph node cells (PLNC) protect islet transplants in Non-obese diabetic (NOD) mice. We hypothesized that induced FoxP3 + regulatory T cells (Tregs) were required for long-term islet engraftment. NOD or NOD.NON mice were treated with ALS (antilymphocyte serum) and transplanted with NOR islets +/-PLNC (5 × 10 7). In vivo proliferation and expansion of FoxP3 + Tregs was monitored in spleen and PLN from ALS- and ALS/PLNC-treated recipient mice. Anti-CD25 depletion was used to determine the necessity of Tregs for tolerance. FoxP3 + numbers significantly increased in ALS/PLNC-treated recipients compared to ALS-treated mice. In ALS/PLNC-treated mice, recipient-derived Tregs localized to the transplanted islets, and this was associated with intact, insulin-producing β cells. Proliferation and expansion of FoxP3 + Tregs was markedly increased in PLNC-treated mice with accepted islet grafts, but not in diabetic mice not receiving PLNC. Deletion of Tregs with anti-CD25 antibodies prevented islet graft tolerance and resulted in rejection. Adoptive transfer of Tregs to secondary NOD.scid recipients inhibited autoimmunity by cotransferred NOD effector T cells. Treg expansion induced by ALS/PLNC-treatment promoted long term islet graft survival. Strategies leading to Treg proliferation and localization to the transplant site represent a therapeutic approach to controlling recurrent autoimmunity. This study demonstrates the critical role of recipient regulatory T cell proliferation and expansion in the protection of islet transplants from recurrent autoimmunity.

Original languageEnglish
Pages (from-to)1124-1132
Number of pages9
JournalAmerican Journal of Transplantation
Issue number5
StatePublished - May 2012
Externally publishedYes


  • Antilymphocyte antibodies
  • NOD mice
  • autoimmunity
  • diabetes mellitus
  • donor T cell
  • islet cells
  • regulatory cells


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