Current Transplantation Reports

, Volume 4, Issue 4, pp 270–279 | Cite as

Harnessing Apoptotic Cells for Transplantation Tolerance: Current Status and Future Perspectives

  • Anil Dangi
  • Xunrong LuoEmail author
Immunology (R Fairchild, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Immunology


Purpose of Review

The use of donor apoptotic cells is an emerging therapy for inducing transplantation tolerance. In this review, we will discuss current understanding of mechanisms of this approach, as well as crucial aspects necessary for successful translation of this approach to clinical transplantation.

Recent Findings

Transplantation tolerance by donor apoptotic cells is mediated by their homeostatic interaction with recipient phagocytes and subsequent expansion of suppressor cell populations as well as inhibition of effector T cells via deletion and anergy. To ensure their tolerogenicity, it is critical to procure non-stressed donor cells and to induce and arrest their apoptosis at the appropriate stage prior to their administration. Equally important is the monitoring of dynamics of recipient immunological status and its influences on tolerance efficacy and longevity. Emerging concepts and technologies may significantly streamline tolerogen manufacture and delivery of this approach and smooth its transition to clinical application.


Hijacking homeostatic clearance of donor apoptotic cells is a promising strategy for transplantation tolerance. Timing is now mature for concerted efforts for transitioning this strategy to clinical transplantation.


Apoptotic cells Transplantation Tolerance Suppressor cells Sensitization Nanoparticles 



This work was supported by grants from the National Institutes of Health P01 AI112522 (A.D.), U01 AI102463 (X.L.), and R01 EB009910 (X.L.).

Author Contributions

A.D. and X.L. conceptualized and wrote the manuscript. X.L. edited and finalized the manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, are highlighted as: • Of importance •• Of major importance

  1. 1.
    Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Millan MT, Shizuru JA, et al. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med. 2008;358(4):362–8. CrossRefPubMedGoogle Scholar
  2. 2.
    Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008;358(4):353–61. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Leventhal J, Abecassis M, Miller J, Gallon L, Ravindra K, Tollerud DJ, et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. Sci Transl Med. 2012;4(124):124ra28. Scholar
  4. 4.
    Leventhal JR, Mathew JM, Salomon DR, Kurian SM, Suthanthiran M, Tambur A, et al. Genomic biomarkers correlate with HLA-identical renal transplant tolerance. J Am Soc Nephrol. 2013;24(9):1376–85. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Leventhal J, Abecassis M, Miller J, Gallon L, Tollerud D, Elliott MJ, et al. Tolerance induction in HLA disparate living donor kidney transplantation by donor stem cell infusion: durable chimerism predicts outcome. Transplantation. 2013;95(1):169–76. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    •• Arandjelovic S, Ravichandran KS. Phagocytosis of apoptotic cells in homeostasis. Nat Immunol. 2015;16(9):907–17. This comprehensive review details recent advances in our understanding of the clearance of apoptotic bodies by professional and non-professional cell-types and signaling machinery involved in this process. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Elliott MR, Ravichandran KS. The dynamics of apoptotic cell clearance. Dev Cell. 2016;38(2):147–60. Scholar
  8. 8.
    Henson PM. Dampening inflammation. Nat Immunol. 2005;6(12):1179–81. CrossRefPubMedGoogle Scholar
  9. 9.
    Morelli AE, Larregina AT. Concise review: mechanisms behind apoptotic cell-based therapies against transplant rejection and graft versus host disease. Stem Cells. 2016;34(5):1142–50. CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Oberbarnscheidt MH, Zeng Q, Li Q, Dai H, Williams AL, Shlomchik WD, et al. Non-self recognition by monocytes initiates allograft rejection. J Clin Invest. 2014;124(8):3579–89. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Bittencourt MC, Perruche S, Contassot E, Fresnay S, Baron MH, Angonin R, et al. Intravenous injection of apoptotic leukocytes enhances bone marrow engraftment across major histocompatibility barriers. Blood. 2001;98(1):224–30. CrossRefPubMedGoogle Scholar
  12. 12.
    Sun E, Gao Y, Chen J, Roberts AI, Wang X, Chen Z, et al. Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient. Cell Death Differ. 2004;11(12):1258–64. CrossRefPubMedGoogle Scholar
  13. 13.
    Wang Z, Larregina AT, Shufesky WJ, Perone MJ, Montecalvo A, Zahorchak AF, et al. Use of the inhibitory effect of apoptotic cells on dendritic cells for graft survival via T-cell deletion and regulatory T cells. Am J Transplant. 2006;6(6):1297–311. CrossRefPubMedGoogle Scholar
  14. 14.
    Mougel F, Bonnefoy F, Kury-Paulin S, Borot S, Perruche S, Kantelip B, et al. Intravenous infusion of donor apoptotic leukocytes before transplantation delays allogeneic islet graft rejection through regulatory T cells. Diabetes Metab. 2012;38(6):531–7. CrossRefPubMedGoogle Scholar
  15. 15.
    Wu C, Zhang Y, Jiang Y, Wang Q, Long Y, Wang C, et al. Apoptotic cell administration enhances pancreatic islet engraftment by induction of regulatory T cells and tolerogenic dendritic cells. Cell Mol Immunol. 2013;10(5):393–402. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Perruche S, Kleinclauss F, Bittencourt Mde C, Paris D, Tiberghien P, Saas P. Intravenous infusion of apoptotic cells simultaneously with allogeneic hematopoietic grafts alters anti-donor humoral immune responses. Am J Transplant. 2004;4(8):1361–5. CrossRefPubMedGoogle Scholar
  17. 17.
    Wang Z, Shufesky WJ, Montecalvo A, Divito SJ, Larregina AT, Morelli AE. In situ-targeting of dendritic cells with donor-derived apoptotic cells restrains indirect allorecognition and ameliorates allograft vasculopathy. PLoS One. 2009;4(3):e4940. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    • Wang S, Zhang X, Zhang L, Bryant J, Kheradmand T, Hering BJ, et al. Preemptive tolerogenic delivery of donor antigens for permanent allogeneic islet graft protection. Cell Transplant. 2015;24(6):1155–65. This study defines several important parameters regarding the use of apoptotic cells for transplantation tolerance, including dose optimization, feasibility of using frozen cells, and compatibility with other immunosuppressive drugs. CrossRefPubMedGoogle Scholar
  19. 19.
    Kheradmand T, Wang S, Bryant J, Tasch JJ, Lerret N, Pothoven KL, et al. Ethylenecarbodiimide-fixed donor splenocyte infusions differentially target direct and indirect pathways of allorecognition for induction of transplant tolerance. J Immunol. 2012;189(2):804–12. Scholar
  20. 20.
    Luo X, Pothoven KL, McCarthy D, DeGutes M, Martin A, Getts DR, et al. ECDI-fixed allogeneic splenocytes induce donor-specific tolerance for long-term survival of islet transplants via two distinct mechanisms. Proc Natl Acad Sci U S A. 2008;105(38):14527–32. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Chen G, Kheradmand T, Bryant J, Wang S, Tasch J, Wang JJ, et al. Intragraft CD11b(+) IDO(+) cells mediate cardiac allograft tolerance by ECDI-fixed donor splenocyte infusions. Am J Transplant. 2012;12(11):2920–9. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wang S, Tasch J, Kheradmand T, Ulaszek J, Ely S, Zhang X, et al. Transient B-cell depletion combined with apoptotic donor splenocytes induces xeno-specific T- and B-cell tolerance to islet xenografts. Diabetes. 2013;62(9):3143–50. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Bryant J, Lerret NM, Wang JJ, Kang HK, Tasch J, Zhang Z, et al. Preemptive donor apoptotic cell infusions induce IFN-gamma-producing myeloid-derived suppressor cells for cardiac allograft protection. J Immunol. 2014;192(12):6092–101. Scholar
  24. 24.
    Kang HK, Wang S, Dangi A, Zhang X, Singh A, Zhang L, et al. Differential role of B cells and IL-17 versus IFN-gamma during early and late rejection of pig islet xenografts in mice. Transplantation. 2016;
  25. 25.
    •• Mevorach D, Zuckerman T, Reiner I, Shimoni A, Samuel S, Nagler A, et al. Single infusion of donor mononuclear early apoptotic cells as prophylaxis for graft-versus-host disease in myeloablative HLA-matched allogeneic bone marrow transplantation: a phase I/IIa clinical trial. Biol Blood Marrow Transplant. 2014;20(1):58–65. This clinical trial highlights the safety and potential efficacy of the use of donor apoptotic cells in preventing acute GVHD after allogeneic bone marrow transplantation. CrossRefPubMedGoogle Scholar
  26. 26.
    Voll RE, Herrmann M, Roth EA, Stach C, Kalden JR, Girkontaite I. Immunosuppressive effects of apoptotic cells. Nature. 1997;390(6658):350–1. CrossRefPubMedGoogle Scholar
  27. 27.
    Bonnefoy F, Masson E, Perruche S, Marandin A, Borg C, Radlovic A, et al. Sirolimus enhances the effect of apoptotic cell infusion on hematopoietic engraftment and tolerance induction. Leukemia. 2008;22(7):1430–4. CrossRefPubMedGoogle Scholar
  28. 28.
    Morelli AE, Larregina AT. Apoptotic cell-based therapies against transplant rejection: role of recipient’s dendritic cells. Apoptosis. 2010;15(9):1083–97. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Yamaguchi J, Kanematsu T, Shiku H, Nakayama E. Long-term survival of orthotopic Lewis liver grafts in Wistar Furth rats. Elimination or inactivation of effector CTL and altered antigenicity as possible reasons for tolerance. Transplantation. 1994;57(3):412–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Yamano T, Watanabe S, Hasegawa H, Suzuki T, Abe R, Tahara H, et al. Ex vivo-expanded DCs induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin grafts. Blood. 2011;117(9):2640–8. CrossRefPubMedGoogle Scholar
  31. 31.
    de Kort H, Crul C, van der Wal AM, Schlagwein N, Stax AM, Bruijn JA, et al. Accelerated antibody-mediated graft loss of rodent pancreatic islets after pretreatment with dexamethasone-treated immature donor dendritic cells. Transplantation. 2012;94(9):903–10. CrossRefPubMedGoogle Scholar
  32. 32.
    • Smyth LA, Ratnasothy K, Moreau A, Alcock S, Sagoo P, Meader L, et al. Tolerogenic donor-derived dendritic cells risk sensitization in vivo owing to processing and presentation by recipient APCs. J Immunol. 2013;190(9):4848–60. This study highlights the potential risk of recipient sensitization when using donor tolerogenic dendritic cells for tolerance induction. The data presented in this study suggest that a precise quality control method will be necessary while using donor cells for tolerance induction. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Warren HS, Smyth MJ. NK cells and apoptosis. Immunol Cell Biol. 1999;77(1):64–75. CrossRefPubMedGoogle Scholar
  34. 34.
    Yu G, Xu X, MD V, Kilpatrick ED, Li XC. NK cells promote transplant tolerance by killing donor antigen-presenting cells. J Exp Med. 2006;203(8):1851–8. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    He B. Viruses, endoplasmic reticulum stress, and interferon responses. Cell Death Differ. 2006;13(3):393–403. CrossRefPubMedGoogle Scholar
  36. 36.
    Smith JA. A new paradigm: innate immune sensing of viruses via the unfolded protein response. Front Microbiol. 2014;5:222. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Valadao AL, Aguiar RS, de Arruda LB. Interplay between inflammation and cellular stress triggered by Flaviviridae viruses. Front Microbiol. 2016;7:1233. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Martinon F, Chen X, Lee AH, Glimcher LH. TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nat Immunol. 2010;11(5):411–8. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundback P, et al. Novel role of PKR in inflammasome activation and HMGB1 release. Nature. 2012;488(7413):670–4. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Lee GS, Subramanian N, Kim AI, Aksentijevich I, Goldbach-Mansky R, Sacks DB, et al. The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP. Nature. 2012;492(7427):123–7. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Sano R, Reed JC. ER stress-induced cell death mechanisms. Biochim Biophys Acta. 2013;1833(12):3460–70. CrossRefPubMedGoogle Scholar
  42. 42.
    Knudsen S, Schardt A, Buhl T, Boeckmann L, Schon MP, Neumann C, et al. Enhanced T-cell activation by immature dendritic cells loaded with HSP70-expressing heat-killed melanoma cells. Exp Dermatol. 2010;19(2):108–16. CrossRefPubMedGoogle Scholar
  43. 43.
    Song S, Tan J, Miao Y, Li M, Zhang Q. Crosstalk of autophagy and apoptosis: involvement of the dual role of autophagy under ER stress. J Cell Physiol. 2017;
  44. 44.
    Chong AS, Alegre ML. The impact of infection and tissue damage in solid-organ transplantation. Nature Reviews Immunol. 2012;12(6):459–71. CrossRefGoogle Scholar
  45. 45.
    Fond AM, Ravichandran KS. Clearance of dying cells by phagocytes: mechanisms and implications for disease pathogenesis. Adv Exp Med Biol. 2016;930:25–49. CrossRefPubMedGoogle Scholar
  46. 46.
    Thorp EB. Mechanisms of failed apoptotic cell clearance by phagocyte subsets in cardiovascular disease. Apoptosis. 2010;15(9):1124–36. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Eikmans M, Waanders MM, Roelen DL, van Miert PP, Anholts JD, de Fijter HW, et al. Differential effect of pretransplant blood transfusions on immune effector and regulatory compartments in HLA-sensitized and nonsensitized recipients. Transplantation. 2010;90(11):1192–9. CrossRefPubMedGoogle Scholar
  48. 48.
    • Burns AM, Chong AS. Alloantibodies prevent the induction of transplantation tolerance by enhancing alloreactive T cell priming. J Immunol. 2011;186(1):214–221. doi:10.4049/jimmunol.1001172. This study highlights the ability of alloantibodies to function as opsonins to prevent transplantation tolerance by donor-specific transfusion in sensitized recipients. Google Scholar
  49. 49.
    Saethre M, Schneider MK, Lambris JD, Magotti P, Haraldsen G, Seebach JD, et al. Cytokine secretion depends on Galalpha(1,3)Gal expression in a pig-to-human whole blood model. J Immunol. 2008;180(9):6346–53. Scholar
  50. 50.
    Burns AM, Ma L, Li Y, Yin D, Shen J, Xu J, et al. Memory alloreactive B cells and alloantibodies prevent anti-CD154-mediated allograft acceptance. J Immunol. 2009;182(3):1314–24. Scholar
  51. 51.
    Chong AS, Sciammas R. Memory B cells in transplantation. Transplantation. 2015;99(1):21–8. CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Valujskikh A, Pantenburg B, Heeger PS. Primed allospecific T cells prevent the effects of costimulatory blockade on prolonged cardiac allograft survival in mice. Am J Transplant. 2002;2(6):501–9. CrossRefPubMedGoogle Scholar
  53. 53.
    Adams AB, Williams MA, Jones TR, Shirasugi N, Durham MM, Kaech SM, et al. Heterologous immunity provides a potent barrier to transplantation tolerance. J Clin Invest. 2003;111(12):1887–95. CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Vu MD, Clarkson MR, Yagita H, Turka LA, Sayegh MH, Li XC. Critical, but conditional, role of OX40 in memory T cell-mediated rejection. J Immunol. 2006;176(3):1394–401. Scholar
  55. 55.
    Yamaura K, Boenisch O, Watanabe T, Ueno T, Vanguri V, Yang J, et al. Differential requirement of CD27 costimulatory signaling for naive versus alloantigen-primed effector/memory CD8+ T cells. Am J Transplant. 2010;10(5):1210–20. CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Ge W, Jiang J, Arp J, Liu W, Garcia B, Wang H. Regulatory T-cell generation and kidney allograft tolerance induced by mesenchymal stem cells associated with indoleamine 2,3-dioxygenase expression. Transplantation. 2010;90(12):1312–20. CrossRefPubMedGoogle Scholar
  57. 57.
    Zhang Q, Chen Y, Fairchild RL, Heeger PS, Valujskikh A. Lymphoid sequestration of alloreactive memory CD4 T cells promotes cardiac allograft survival. J Immunol. 2006;176(2):770–7. Scholar
  58. 58.
    Ramsey H, Pilat N, Hock K, Klaus C, Unger L, Schwarz C, et al. Anti-LFA-1 or rapamycin overcome costimulation blockade-resistant rejection in sensitized bone marrow recipients. Transpl Int. 2013;26(2):206–18. CrossRefPubMedGoogle Scholar
  59. 59.
    Miller ML, Daniels MD, Wang T, Wang Y, Xu J, Yin D, et al. Tracking of TCR-Tg T cells reveals multiple mechanisms maintain cardiac transplant tolerance in mice. American J Transplant. 2016;16(10):2854–64. CrossRefGoogle Scholar
  60. 60.
    Besancon A, Baas M, Goncalves T, Valette F, Waldmann H, Chatenoud L, et al. The induction and maintenance of transplant tolerance engages both regulatory and anergic CD4+ T cells. Front Immunol. 2017;8:218. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Parekh VV, Lalani S, Kim S, Halder R, Azuma M, Yagita H, et al. PD-1/PD-L blockade prevents anergy induction and enhances the anti-tumor activities of glycolipid-activated invariant NKT cells. J Immunol. 2009;182(5):2816–26. Scholar
  62. 62.
    Baas M, Besancon A, Goncalves T, Valette F, Yagita H, Sawitzki B, et al. TGFbeta-dependent expression of PD-1 and PD-L1 controls CD8(+) T cell anergy in transplant tolerance. elife. 2016;5:e08133. CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Wang T, Ahmed EB, Chen L, Xu J, Tao J, Wang CR, et al. Infection with the intracellular bacterium, Listeria monocytogenes, overrides established tolerance in a mouse cardiac allograft model. Am J Transplant. 2010;10(7):1524–33. CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    • Miller ML, Daniels MD, Wang T, Chen J, Young J, Xu J, et al. Spontaneous restoration of transplantation tolerance after acute rejection. Nat Commun. 2015;6:7566. This study demonstrates that after abrogation of transplantation tolerance by infection, donor-specific tolerant state can re-emerge, allowing spontaneous acceptance of a donor-matched second transplant. The study demonstrates a setting in which memory of allograft tolerance exists during tolerance maintenance. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Young JS, Daniels MD, Miller ML, Wang T, Zhong R, Yin D, et al. Erosion of transplantation tolerance after infection. Am J Transplant. 2017;17(1):81–90. CrossRefPubMedGoogle Scholar
  66. 66.
    Pace L, Vitale S, Dettori B, Palombi C, La Sorsa V, Belardelli F, et al. APC activation by IFN-alpha decreases regulatory T cell and enhances Th cell functions. J Immunol. 2010;184(11):5969–79. Scholar
  67. 67.
    Raker V, Steinbrink K. Research in practice: the impact of interferon-alpha therapy on immune tolerance. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology: JDDG. 2014;12(4):315–9. PubMedGoogle Scholar
  68. 68.
    Perruche S, Zhang P, Liu Y, Saas P, Bluestone JA, Chen W. CD3-specific antibody-induced immune tolerance involves transforming growth factor-beta from phagocytes digesting apoptotic T cells. Nat Med. 2008;14(5):528–35. CrossRefPubMedGoogle Scholar
  69. 69.
    • Kasagi S, Zhang P, Che L, Abbatiello B, Maruyama T, Nakatsukasa H, et al. In vivo-generated antigen-specific regulatory T cells treat autoimmunity without compromising antibacterial immune response. Science Translat Med. 2014;6(241):241ra78. This study presents an attractive approach for inducing antigen-specific tolerance via in vivo cell-death in a disease model of autoimmunity. This study paves a way for inducing transplantation tolerance in which several variables pertaining the donor and the ex vivo-manufactured donor apoptotic cells can be overcome. CrossRefGoogle Scholar
  70. 70.
    Martin AJ, McCarthy D, Waltenbaugh C, Goings G, Luo X, Miller SD. Ethylenecarbodiimide-treated splenocytes carrying male CD4 epitopes confer histocompatibility Y chromosome antigen transplant protection by inhibiting CD154 upregulation. J Immunol. 2010;185(6):3326–36. Scholar
  71. 71.
    • Bryant J, Hlavaty KA, Zhang X, Yap WT, Zhang L, Shea LD, et al. Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation. Biomaterials. 2014;35(31):8887–94. This report presents that nanoparticles can be utilized as carriers for the delivery of alloantigens in lieu of intact donor cells. This approach when combined with the immunosuppressive drug rapamycin induces robust transplantation tolerance. CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Hlavaty KA, McCarthy DP, Saito E, Yap WT, Miller SD, Shea LD. Tolerance induction using nanoparticles bearing HY peptides in bone marrow transplantation. Biomaterials. 2015;76:1–10. CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Roberts RA, Eitas TK, Byrne JD, Johnson BM, Short PJ, McKinnon KP, et al. Towards programming immune tolerance through geometric manipulation of phosphatidylserine. Biomaterials. 2015;72:1–10. CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Tang L, Azzi J, Kwon M, Mounayar M, Tong R, Yin Q, et al. Immunosuppressive activity of size-controlled PEG-PLGA nanoparticles containing encapsulated cyclosporine A. J Transp Secur. 2012;2012:896141. Google Scholar
  75. 75.
    Solhjou Z, Uehara M, Bahmani B, Maarouf OH, Ichimura T, Brooks CR, et al. Novel application of localized nanodelivery of anti-interleukin-6 protects organ transplant from ischemia-reperfusion injuries. Am J Transplant. 2017;
  76. 76.
    • Tostanoski LH, Chiu YC, Gammon JM, Simon T, Andorko JI, Bromberg JS, et al. Reprogramming the local lymph node microenvironment promotes tolerance that is systemic and antigen specific. Cell Rep. 2016;16(11):2940–52. This is an elegant study which highlights that local delivery of autoantigens to lymph nodes via nanocarriers is highly efficacious in inducing systemic tolerance in the EAE model. The efficacy of this approach now needs to be evaluated in settings of transplantation. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Center for Kidney Research and Therapeutics, Feinberg Cardiovascular Research InstituteNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Division of Nephrology and Hypertension, Department of MedicineNorthwestern University Feinberg School of MedicineChicagoUSA
  3. 3.Comprehensive Transplant CenterNorthwestern University Feinberg School of MedicineChicagoUSA

Personalised recommendations