Division of Transplantation, Department of Surgery, University of Maryland School of Medicine, University of Maryland, Baltimore, MD, USA.
Am J Transplant. 2012 May;12(5):1124-32. doi: 10.1111/j.1600-6143.2011.03943.x. Epub 2012 Feb 2.
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.
供体胰腺淋巴结细胞 (PLNC) 可保护非肥胖型糖尿病 (NOD) 小鼠的胰岛移植物。我们假设诱导的 FoxP3(+)调节性 T 细胞 (Treg) 是胰岛长期植入所必需的。用 ALS（抗淋巴细胞血清）处理 NOD 或 NOD.NON 小鼠，并移植 NOR 胰岛 +/-PLNC（5×10(7) ）。在体内，监测 ALS 和 ALS/PLNC 处理的受者小鼠脾和 PLN 中 FoxP3(+)Treg 的增殖和扩增。用抗 CD25 耗竭来确定 Treg 对耐受的必要性。与 ALS 处理的小鼠相比，ALS/PLNC 处理的受者中 FoxP3(+)数量显著增加。在 ALS/PLNC 处理的小鼠中，受者来源的 Treg 定位于移植的胰岛，这与完整的、产生胰岛素的β细胞有关。接受胰岛移植物的 PLNC 处理的小鼠中 FoxP3(+)Treg 的增殖和扩增明显增加，但未接受 PLNC 的糖尿病小鼠则没有。用抗 CD25 抗体耗竭 Treg 可防止胰岛移植物耐受，并导致排斥。将 Treg 过继转移到继发的 NOD.scid 受者中，通过共转导的 NOD 效应 T 细胞抑制自身免疫。ALS/PLNC 处理诱导的 Treg 扩增促进胰岛移植物的长期存活。导致 Treg 增殖和定位于移植部位的策略代表了控制复发性自身免疫的一种治疗方法。
