Details

Autor(en) / Beteiligte

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

Titel

Endogenous Expansion of Regulatory T Cells Leads to Long‐Term Islet Graft Survival in Diabetic NOD Mice

Ist Teil von

• American journal of transplantation, 2012-05, Vol.12 (5), p.1124-1132

Ort / Verlag

Malden, USA: Blackwell Publishing Inc

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 × 107). 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.