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

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

DOI: 10.1111/J.1600-6143.2011.03943.X

关键词:

摘要: Donor pancreatic lymph node cells (PLNC) protect islet transplants in Non-obese diabetic (NOD) mice. We hypothesized that induced FoxP3+ regulatory T (Tregs) were required for long-term engraftment. NOD or NOD.NON mice treated with ALS (antilymphocyte serum) and transplanted NOR islets +/–PLNC (5 × 107). In vivo proliferation expansion of Tregs was monitored spleen PLN from ALS- ALS/PLNC-treated recipient Anti-CD25 depletion used to determine the necessity tolerance. numbers significantly increased recipients compared ALS-treated mice, recipient-derived localized islets, this associated intact, insulin-producing β cells. Proliferation markedly PLNC-treated accepted grafts, but not receiving PLNC. Deletion anti-CD25 antibodies prevented graft tolerance resulted rejection. Adoptive transfer secondary NOD.scid inhibited autoimmunity by cotransferred effector Treg ALS/PLNC-treatment promoted long term survival. Strategies leading localization transplant site represent a therapeutic approach controlling recurrent autoimmunity.

参考文章(42)
Anya Schneider, Mary Rieck, Srinath Sanda, Catherine Pihoker, Carla Greenbaum, Jane H. Buckner, The effector T cells of diabetic subjects are resistant to regulation via CD4+ FOXP3+ regulatory T cells. Journal of Immunology. ,vol. 181, pp. 7350- 7355 ,(2008) , 10.4049/JIMMUNOL.181.10.7350
Veronika Szanya, Joerg Ermann, Cariel Taylor, Claire Holness, C. Garrison Fathman, The Subpopulation of CD4+CD25+ Splenocytes That Delays Adoptive Transfer of Diabetes Expresses L-Selectin and High Levels of CCR7 The Journal of Immunology. ,vol. 169, pp. 2461- 2465 ,(2002) , 10.4049/JIMMUNOL.169.5.2461
Baolin Liu, Jianqiang Hao, Yisheng Pan, Bin Luo, Britt Westgard, Yves Heremans, David E. R. Sutherland, Bernhard J. Hering, Zhiguang Guo, Increasing donor chimerism and inducing tolerance to islet allografts by post-transplant donor lymphocyte infusion. American Journal of Transplantation. ,vol. 6, pp. 933- 946 ,(2006) , 10.1111/J.1600-6143.2006.01283.X
Keisuke Minamimura, Wenda Gao, Takashi Maki, CD4+ Regulatory T Cells Are Spared from Deletion by Antilymphocyte Serum, a Polyclonal Anti-T Cell Antibody Journal of Immunology. ,vol. 176, pp. 4125- 4132 ,(2006) , 10.4049/JIMMUNOL.176.7.4125
Tao Wu, Brett Levay-Young, Neal Heuss, Hakan Sozen, Nicole Kirchhof, David E. R. Sutherland, Bernhard Hering, Zhiguang Guo, Inducing tolerance to MHC-matched allogeneic islet grafts in diabetic NOD mice by simultaneous islet and bone marrow transplantation under nonirradiative and nonmyeloablative conditioning therapy. Transplantation. ,vol. 74, pp. 22- 27 ,(2002) , 10.1097/00007890-200207150-00005
Paolo Monti, Miriam Scirpoli, Paola Maffi, Nadia Ghidoli, Francesca De Taddeo, Federico Bertuzzi, Lorenzo Piemonti, Marika Falcone, Antonio Secchi, Ezio Bonifacio, Islet transplantation in patients with autoimmune diabetes induces homeostatic cytokines that expand autoreactive memory T cells Journal of Clinical Investigation. ,vol. 118, pp. 1806- 1814 ,(2008) , 10.1172/JCI35197
Boris Nikolic, Takashi Onoe, Yasuo Takeuchi, Zain Khalpey, Valeria Primo, Igor Leykin, R Neal Smith, Megan Sykes, Distinct requirements for achievement of allotolerance versus reversal of autoimmunity via nonmyeloablative mixed chimerism induction in NOD mice. Transplantation. ,vol. 89, pp. 23- 32 ,(2010) , 10.1097/TP.0B013E3181C4692E
Jun Yamanouchi, Dan Rainbow, Pau Serra, Sarah Howlett, Kara Hunter, Valerie E S Garner, Andrea Gonzalez-Munoz, Jan Clark, Riitta Veijola, Rose Cubbon, Show-Ling Chen, Raymond Rosa, Anne Marie Cumiskey, David V Serreze, Simon Gregory, Jane Rogers, Paul A Lyons, Barry Healy, Luc J Smink, John A Todd, Laurence B Peterson, Linda S Wicker, Pere Santamaria, Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity Nature Genetics. ,vol. 39, pp. 329- 337 ,(2007) , 10.1038/NG1958
A. J. Wu, H. Hua, S. H. Munson, H. O. McDevitt, Tumor necrosis factor-α regulation of CD4+C25+ T cell levels in NOD mice Proceedings of the National Academy of Sciences of the United States of America. ,vol. 99, pp. 12287- 12292 ,(2002) , 10.1073/PNAS.172382999
Xingmin Feng, Sachiko Kajigaya, Elena E. Solomou, Keyvan Keyvanfar, Xiuli Xu, Nalini Raghavachari, Peter J. Munson, Thomas M. Herndon, Jichun Chen, Neal S. Young, Rabbit ATG but not horse ATG promotes expansion of functional CD4+CD25highFOXP3+ regulatory T cells in vitro. Blood. ,vol. 111, pp. 3675- 3683 ,(2007) , 10.1182/BLOOD-2008-01-130146