Review Article | Published:

Composite tissue allotransplantation: opportunities and challenges

Cellular & Molecular Immunology (2019) | Download Citation


Vascularized composite allotransplants (VCAs) have unique properties because of diverse tissue components transplanted en mass as a single unit. In addition to surgery, this type of transplant also faces enormous immunological challenges that demand a detailed analysis of all aspects of alloimmune responses, organ preservation, and injury, as well as the immunogenicity of various tissues within the VCA grafts to further improve graft and patient outcomes. Moreover, the side effects of long-term immunosuppression for VCA patients need to be carefully balanced with the potential benefit of a non-life-saving procedure. In this review article, we provide a comprehensive update on limb and face transplantation, with a specific emphasis on the alloimmune responses to VCA, established and novel immunosuppressive treatments, and patient outcomes.

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  1. 1.

    Shores, J. T., Brandacher, G. & Lee, W. P. Hand and upper extremity transplantation: an update of outcomes in the worldwide experience. Plast. Reconstr. Surg. 135, 351e–360e (2015).

  2. 2.

    Brannstrom, M. Womb transplants with live births: an update and the future. Expert. Opin. Biol. Ther. 17, 1105–1112 (2017).

  3. 3.

    Sinha, I. & Pomahac, B. Split rejection in vascularized composite allotransplantation. Eplasty 13, e53 (2013).

  4. 4.

    Petruzzo, P. & Dubernard, J. M. The International Registry on Hand and Composite Tissue allotransplantation. Clin. Transpl. 247–253 (2011) PMID: 22755418.

  5. 5.

    Fischer, S. et al. Acute rejection in vascularized composite allotransplantation. Curr. Opin. Organ Transplant. 19, 531–544 (2014).

  6. 6.

    Mathes, D. W. et al. Split tolerance to a composite tissue allograft in a swine model. Transplantation 75, 25–31 (2003).

  7. 7.

    Kaufman, C. L. et al. Immunobiology in VCA. Transpl. Int. 29, 644–654 (2016).

  8. 8.

    Kanitakis, J. The challenge of dermatopathological diagnosis of composite tissue allograft rejection: a review. J. Cutan. Pathol. 35, 738–744 (2008).

  9. 9.

    Kueckelhaus, M. et al. Utility of sentinel flaps in assessing facial allograft rejection. Plast. Reconstr. Surg. 135, 250–258 (2015).

  10. 10.

    Kueckelhaus, M. et al. Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration. Transpl. Int. 29, 655–662 (2016).

  11. 11.

    Clark, R. A. et al. The vast majority of CLA + T cells are resident in normal skin. J. Immunol. 176, 4431–4439 (2006).

  12. 12.

    Clark, R. A. Skin-resident T cells: the ups and downs of on site immunity. J. Invest. Dermatol. 130, 362–370 (2010).

  13. 13.

    Li, J., Olshansky, M., Carbone, F. R. & Ma, J. Z. Transcriptional analysis of T cells resident in human skin. PLoS ONE 11, e0148351 (2016).

  14. 14.

    Clark, R. A. et al. Skin effector memory T cells do not recirculate and provide immune protection in alemtuzumab-treated CTCL patients. Sci. Transl. Med. 4, 117ra117 (2012).

  15. 15.

    Jiang, X. et al. Skin infection generates non-migratory memory CD8 + T(RM) cells providing global skin immunity. Nature 483, 227–231 (2012).

  16. 16.

    Egawa, G. & Kabashima, K. Skin as a peripheral lymphoid organ: revisiting the concept of skin-associated lymphoid tissues. J. Invest. Dermatol. 131, 2178–2185 (2011).

  17. 17.

    Chadha, R., Leonard, D. A., Kurtz, J. M. & Cetrulo, C. L. Jr The unique immunobiology of the skin: implications for tolerance of vascularized composite allografts. Curr. Opin. Organ Transplant. 19, 566–572 (2014).

  18. 18.

    Lian, C. G. et al. Biomarker evaluation of face transplant rejection: association of donor T cells with target cell injury. Mod. Pathol. 27, 788–799 (2014).

  19. 19.

    Mathes, D. W. et al. Tolerance to vascularized composite allografts in canine mixed hematopoietic chimeras. Transplantation 92, 1301–1308 (2011).

  20. 20.

    Hettiaratchy, S. et al. Tolerance to composite tissue allografts across a major histocompatibility barrier in miniature swine. Transplantation 77, 514–521 (2004).

  21. 21.

    Bhan, A. K., Mihm, M. C. Jr. & Dvorak, H. F. T cell subsets in allograft rejection. In situ characterization of T cell subsets in human skin allografts by the use of monoclonal antibodies. J. Immunol. 129, 1578–1583 (1982).

  22. 22.

    Sarhane, K. A. et al. Diagnosing skin rejection in vascularized composite allotransplantation: advances and challenges. Clin. Transplant. 28, 277–285 (2014).

  23. 23.

    Schlapbach, C. et al. Human TH9 cells are skin-tropic and have autocrine and paracrine proinflammatory capacity. Sci. Transl. Med. 6, 219ra218 (2014).

  24. 24.

    Laggner, U. et al. Identification of a novel proinflammatory human skin-homing Vgamma9Vdelta2 T cell subset with a potential role in psoriasis. J. Immunol. 187, 2783–2793 (2011).

  25. 25.

    Issa, F. Vascularized composite allograft-specific characteristics of immune responses. Transpl. Int. 29, 672–681 (2016).

  26. 26.

    Taflin, C., Charron, D., Glotz, D. & Mooney, N. Immunological function of the endothelial cell within the setting of organ transplantation. Immunol. Lett. 139, 1–6 (2011).

  27. 27.

    Cines, D. B. et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91, 3527–3561 (1998).

  28. 28.

    Pober, J. S., Kluger, M. S. & Schechner, J. S. Human endothelial cell presentation of antigen and the homing of memory/effector T cells to skin. Ann. N. Y. Acad. Sci. 941, 12–25 (2001).

  29. 29.

    Karmann, K., Hughes, C. C., Fanslow, W. C. & Pober, J. S. Endothelial cells augment the expression of CD40 ligand on newly activated human CD4 + T cells through a CD2/LFA-3 signaling pathway. Eur. J. Immunol. 26, 610–617 (1996).

  30. 30.

    Karmann, K., Hughes, C. C., Schechner, J., Fanslow, W. C. & Pober, J. S. CD40 on human endothelial cells: inducibility by cytokines and functional regulation of adhesion molecule expression. Proc. Natl Acad. Sci. USA 92, 4342–4346 (1995).

  31. 31.

    Pober, J. S. & Cotran, R. S. Cytokines and endothelial cell biology. Physiol. Rev. 70, 427–451 (1990).

  32. 32.

    Sprague, A. H. & Khalil, R. A. Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem. Pharmacol. 78, 539–552 (2009).

  33. 33.

    Rosenberg, A. S. & Singer, A. Cellular basis of skin allograft rejection: an in vivo model of immune-mediated tissue destruction. Annu. Rev. Immunol. 10, 333–358 (1992).

  34. 34.

    Hautz, T. et al. The impact of skin type and area on skin rejection in limb transplantation. VCA 1, 42–49 (2014).

  35. 35.

    Barth, R. N. et al. Vascularized bone marrow-based immunosuppression inhibits rejection of vascularized composite allografts in nonhuman primates. Am. J. Transplant. 11, 1407–1416 (2011).

  36. 36.

    Ramirez, A. E. et al. A novel rat full-thickness hemi-abdominal wall/hindlimb osteomyocutaneous combined flap: influence of allograft mass and vascularized bone marrow content on vascularized composite allograft survival. Transpl. Int. 27, 977–986 (2014).

  37. 37.

    Snider, M. E., Armstrong, L., Hudson, J. L. & Steinmuller, D. In vitro and in vivo cytotoxicity of T cells cloned from rejecting allografts. Transplantation 42, 171–177 (1986).

  38. 38.

    Noble, R. L. & Steinmuller, D. Blocking of interleukin-2 production, but not the tissue destruction induced by cytotoxic T cells, by cyclosporine. Transplantation 47, 322–326 (1989).

  39. 39.

    Lopdrup, R. G. et al. Seasonal variability precipitating hand transplant rejection? Transplantation 101, e313 (2017).

  40. 40.

    Engebretsen, K. A., Johansen, J. D., Kezic, S., Linneberg, A. & Thyssen, J. P. The effect of environmental humidity and temperature on skin barrier function and dermatitis. J. Eur. Acad. Dermatol. Venereol. 30, 223–249 (2016).

  41. 41.

    MacMurray, J. P., Barker, J. P., Armstrong, J. D., Bozzetti, L. P. & Kuhn, I. N. Circannual changes in immune function. Life Sci. 32, 2363–2370 (1983).

  42. 42.

    Valvis, S. M., Waithman, J., Wood, F. M., Fear, M. W. & Fear, V. S. The immune response to skin trauma is dependent on the etiology of injury in a mouse model of burn and excision. J. Invest. Dermatol. 135, 2119–2128 (2015).

  43. 43.

    Gregorio, J. et al. Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. J. Exp. Med. 207, 2921–2930 (2010).

  44. 44.

    Guiducci, C. et al. Autoimmune skin inflammation is dependent on plasmacytoid dendritic cell activation by nucleic acids via TLR7 and TLR9. J. Exp. Med. 207, 2931–2942 (2010).

  45. 45.

    Desch, A. N. et al. CD103 + pulmonary dendritic cells preferentially acquire and present apoptotic cell-associated antigen. J. Exp. Med. 208, 1789–1797 (2011).

  46. 46.

    Cao, Q. et al. CD103 + dendritic cells elicit CD8 + T cell responses to accelerate kidney injury in adriamycin nephropathy. J. Am. Soc. Nephrol. 27, 1344–1360 (2016).

  47. 47.

    Azukizawa, H. et al. Induction of T-cell-mediated skin disease specific for antigen transgenically expressed in keratinocytes. Eur. J. Immunol. 33, 1879–1888 (2003).

  48. 48.

    Chakraborty, R. et al. CD8( + ) lineage dendritic cells determine adaptive immune responses to inflammasome activation upon sterile skin injury. Exp. Dermatol. 27, 71–79 (2018).

  49. 49.

    Kennedy-Crispin, M. et al. Human keratinocytes’ response to injury upregulates CCL20 and other genes linking innate and adaptive immunity. J. Invest. Dermatol. 132, 105–113 (2012).

  50. 50.

    Paradis, T. J., Cole, S. H., Nelson, R. T. & Gladue, R. P. Essential role of CCR6 in directing activated T cells to the skin during contact hypersensitivity. J. Invest. Dermatol. 128, 628–633 (2008).

  51. 51.

    Le Borgne, M. et al. Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8 + T cell crosspriming in vivo. Immunity 24, 191–201 (2006).

  52. 52.

    Zaba, L. C. et al. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J. Exp. Med. 204, 3183–3194 (2007).

  53. 53.

    Zhou, L. et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat. Immunol. 8, 967–974 (2007).

  54. 54.

    Oberhuber, R. et al. CD11c + dendritic cells accelerate the rejection of older cardiac transplants via interleukin-17A. Circulation 132, 122–131 (2015).

  55. 55.

    Lee, E. et al. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J. Exp. Med. 199, 125–130 (2004).

  56. 56.

    Friedman, O. et al. Immunological and inflammatory mapping of vascularized composite allograft rejection processes in a rat model. PLoS ONE 12, e0181507 (2017).

  57. 57.

    Alegre, M. L., Goldstein, D. R. & Chong, A. S. Toll-like receptor signaling in transplantation. Curr. Opin. Organ Transplant. 13, 358–365 (2008).

  58. 58.

    Goldstein, D. R., Tesar, B. M., Akira, S. & Lakkis, F. G. Critical role of the Toll-like receptor signal adaptor protein MyD88 in acute allograft rejection. J. Clin. Invest. 111, 1571–1578 (2003).

  59. 59.

    Bianchi, M. E. DAMPs, PAMPs and alarmins: all we need to know about danger. J. Leukoc. Biol. 81, 1–5 (2007).

  60. 60.

    Oppenheim, J. J., Tewary, P., de la Rosa, G. & Yang, D. Alarmins initiate host defense. Adv. Exp. Med. Biol. 601, 185–194 (2007).

  61. 61.

    Moussion, C., Ortega, N. & Girard, J. P. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel ‘alarmin’? PLoS ONE 3, e3331 (2008).

  62. 62.

    Forster, R., Braun, A. & Worbs, T. Lymph node homing of T cells and dendritic cells via afferent lymphatics. Trends Immunol. 33, 271–280 (2012).

  63. 63.

    Zampell, J. C. et al. Regulation of adipogenesis by lymphatic fluid stasis: part I. Adipogenesis, fibrosis, and inflammation. Plast. Reconstr. Surg. 129, 825–834 (2012).

  64. 64.

    Datta, N., Devaney, S. G., Busuttil, R. W., Azari, K. & Kupiec-Weglinski, J. W. Prolonged cold ischemia time results in local and remote organ dysfunction in a murine model of vascularized composite transplantation. Am. J. Transplant. 17, 2572–2579 (2017).

  65. 65.

    Tasigiorgos, S. et al. Face transplantation-current status and future developments. Transpl. Int. 31, 677–688 (2018).

  66. 66.

    Landin, L. et al. Outcomes with respect to disabilities of the upper limb after hand allograft transplantation: a systematic review. Transpl. Int. 25, 424–432 (2012).

  67. 67.

    Fries, C. A. et al. A hyperbaric warm perfusion system preserves tissue composites ex vivo and delays the onset of acute rejection. J. Reconstr. Microsurg. 35, 97–107 (2018).

  68. 68.

    Morris, P. et al. Face transplantation: a review of the technical, immunological, psychological and clinical issues with recommendations for good practice. Transplantation 83, 109–128 (2007).

  69. 69.

    Petruzzo, P. et al. Clinicopathological findings of chronic rejection in a face grafted patient. Transplantation 99, 2644–2650 (2015).

  70. 70.

    Morelon, E. et al. Face transplantation: partial graft loss of the first case 10 years later. Am. J. Transplant. 17, 1935–1940 (2017).

  71. 71.

    Kanitakis, J. et al. Chronic rejection in human vascularized composite allotransplantation (hand and face recipients): an update. Transplantation 100, 2053–2061 (2016).

  72. 72.

    Weissenbacher, A. et al. Antibody-mediated rejection in hand transplantation. Transpl. Int. 27, e13–e17 (2014).

  73. 73.

    Hautz, T. et al. Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts. Transpl. Int. 27, 966–976 (2014).

  74. 74.

    Krezdorn, N. et al. Chronic rejection of human face allografts. Am. J. Transplant. 18, 1–10 (2018).

  75. 75.

    Bakker, R. C. et al. Early interstitial accumulation of collagen type I discriminates chronic rejection from chronic cyclosporine nephrotoxicity. J. Am. Soc. Nephrol. 14, 2142–2149 (2003).

  76. 76.

    Cendales, L. C. et al. The Banff 2007 working classification of skin-containing composite tissue allograft pathology. Am. J. Transplant. 8, 1396–1400 (2008).

  77. 77.

    Lindholm, A. et al. The impact of acute rejection episodes on long-term graft function and outcome in 1347 primary renal transplants treated by 3 cyclosporine regimens. Transplantation 56, 307–315 (1993).

  78. 78.

    Matas, A. J., Gillingham, K. J., Payne, W. D. & Najarian, J. S. The impact of an acute rejection episode on long-term renal allograft survival (t1/2). Transplantation 57, 857–859 (1994).

  79. 79.

    Unadkat, J. V. et al. Composite tissue vasculopathy and degeneration following multiple episodes of acute rejection in reconstructive transplantation. Am. J. Transplant. 10, 251–261 (2010).

  80. 80.

    Schneeberger, S. et al. Cytomegalovirus-related complications in human hand transplantation. Transplantation 80, 441–447 (2005).

  81. 81.

    Barker, J. H. et al. Investigation of risk acceptance in facial transplantation. Plast. Reconstr. Surg. 118, 663–670 (2006).

  82. 82.

    Lopez, M. M. et al. Long-term problems related to immunosuppression. Transpl. Immunol. 17, 31–35 (2006).

  83. 83.

    Pomahac, B., Gobble, R. M. & Schneeberger, S. Facial and hand allotransplantation. Cold Spring Harb. Perspect. Med. 4 (2014).

  84. 84.

    Brenner, M. J., Tung, T. H., Jensen, J. N. & Mackinnon, S. E. The spectrum of complications of immunosuppression: is the time right for hand transplantation? J. Bone Joint Surg. Am. 84-a, 1861–1870 (2002).

  85. 85.

    Conrad, A. et al. Epstein-Barr virus-associated smooth muscle tumors in a composite tissue allograft and a pediatric liver transplant recipient. Transpl. Infect. Dis. 15, E182–E186 (2013).

  86. 86.

    Madani, H., Hettiaratchy, S., Clarke, A. & Butler, P. E. Immunosuppression in an emerging field of plastic reconstructive surgery: composite tissue allotransplantation. J. Plast. Reconstr. Aesthet. Surg. 61, 245–249 (2008).

  87. 87.

    Siemionow, M. & Ozturk, C. Face transplantation: outcomes, concerns, controversies, and future directions. J. Craniofac. Surg. 23, 254–259 (2012).

  88. 88.

    Knoll, B. M. et al. Infections following facial composite tissue allotransplantation–single center experience and review of the literature. Am. J. Transplant. 13, 770–779 (2013).

  89. 89.

    Gordon, C. R., Avery, R. K., Abouhassan, W. & Siemionow, M. Cytomegalovirus and other infectious issues related to face transplantation: specific considerations, lessons learned, and future recommendations. Plast. Reconstr. Surg. 127, 1515–1523 (2011).

  90. 90.

    Hammond, S. P. Infections in composite tissue allograft recipients. Infect. Dis. Clin. North Am. 27, 379–393 (2013).

  91. 91.

    Broyles, J. M. et al. Characterization, prophylaxis, and treatment of infectious complications in craniomaxillofacial and upper extremity allotransplantation: a multicenter perspective. Plast. Reconstr. Surg. 133, 543e–551e (2014).

  92. 92.

    Avery, R. K. Update on infections in composite tissue allotransplantation. Curr. Opin. Organ Transplant. 18, 659–664 (2013).

  93. 93.

    Barret, J. P. et al. Full face transplant: the first case report. Ann. Surg. 254, 252–256 (2011).

  94. 94.

    Cavadas, P. C., Ibanez, J., Thione, A. & Alfaro, L. Bilateral trans-humeral arm transplantation: result at 2 years. Am. J. Transplant. 11, 1085–1090 (2011).

  95. 95.

    Hricik, D. E. et al. Long-term graft outcomes after steroid withdrawal in African American kidney transplant recipients receiving sirolimus and tacrolimus. Transplantation 83, 277–281 (2007).

  96. 96.

    Augustine, J. J. & Hricik, D. E. Are maintenance corticosteroids no longer necessary after kidney transplantation? Clin. J. Am. Soc. Nephrol. 7, 383–384 (2012).

  97. 97.

    Kaufman, C. L. et al. Graft vasculopathy in clinical hand transplantation. Am. J. Transplant. 12, 1004–1016 (2012).

  98. 98.

    Kim, E. J. et al. Costimulation blockade alters germinal center responses and prevents antibody-mediated rejection. Am. J. Transplant. 14, 59–69 (2014).

  99. 99.

    Vincenti, F. et al. Belatacept and long-term outcomes in kidney transplantation. N. Engl. J. Med. 374, 333–343 (2016).

  100. 100.

    Grahammer, J. et al. Benefits and limitations of belatacept in 4 hand-transplanted patients. Am. J. Transplant. 17, 3228–3235 (2017).

  101. 101.

    Olariu, R. et al. Intra-graft injection of tacrolimus promotes survival of vascularized composite allotransplantation. J. Surg. Res. 218, 49–57 (2017).

  102. 102.

    Ravindra, K. V. et al. Hand transplantation in the United States: experience with 3 patients. Surgery 144, 638–643 (2008). discussion 643–644.

  103. 103.

    Feturi, F. G. et al. Mycophenolic acid for topical immunosuppression in vascularized composite allotransplantation: optimizing formulation and preliminary evaluation of bioavailability and pharmacokinetics. Front. Surg. 5, 20 (2018).

  104. 104.

    Diaz-Siso, J. R. et al. Initial experience of dual maintenance immunosuppression with steroid withdrawal in vascular composite tissue allotransplantation. Am. J. Transplant. 15, 1421–1431 (2015).

  105. 105.

    Sakaguchi, S. Naturally arising CD4 + regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 22, 531–562 (2004).

  106. 106.

    Issa, F. & Wood, K. J. The potential role for regulatory T-cell therapy in vascularized composite allograft transplantation. Curr. Opin. Organ Transplant. 19, 558–565 (2014).

  107. 107.

    Yang, J. H. & Eun, S. C. Therapeutic application of T regulatory cells in composite tissue allotransplantation. J. Transl. Med. 15, 218 (2017).

  108. 108.

    Sagoo, P. et al. Human regulatory T cells with alloantigen specificity are more potent inhibitors of alloimmune skin graft damage than polyclonal regulatory T cells. Sci. Transl. Med. 3, 83ra42 (2011).

  109. 109.

    Webster, K. E. et al. In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression. J. Exp. Med. 206, 751–760 (2009).

  110. 110.

    Xu, H. et al. Utility of IL-2 complexes in promoting the survival of murine orthotopic forelimb vascularized composite allografts. Transplantation 102, 70–78 (2018).

  111. 111.

    Jindal, R. et al. Spontaneous resolution of acute rejection and tolerance induction with IL-2 fusion protein in vascularized composite allotransplantation. Am. J. Transplant. 15, 1231–1240 (2015).

  112. 112.

    Kuo, Y. R. et al. Prolongation of composite tissue allotransplant survival by treatment with bone marrow mesenchymal stem cells is correlated with T-cell regulation in a swine hind-limb model. Plast. Reconstr. Surg. 127, 569–579 (2011).

  113. 113.

    Kuo, Y. R. et al. Immunomodulatory effects of bone marrow-derived mesenchymal stem cells in a swine hemi-facial allotransplantation model. PLoS ONE 7, e35459 (2012).

  114. 114.

    Lee, W. P. Hand transplantation: evolution of a personal outlook. J. Hand Surg. Am. 42, 286–290 (2017).

  115. 115.

    Carriel, V. et al. Combination of fibrin-agarose hydrogels and adipose-derived mesenchymal stem cells for peripheral nerve regeneration. J. Neural Eng. 10, 026022 (2013).

  116. 116.

    Lopatina, T. et al. Adipose-derived stem cells stimulate regeneration of peripheral nerves: BDNF secreted by these cells promotes nerve healing and axon growth de novo. PLoS ONE 6, e17899 (2011).

  117. 117.

    Liu, G. et al. Transplantation of adipose-derived stem cells for peripheral nerve repair. Int. J. Mol. Med. 28, 565–572 (2011).

  118. 118.

    Plock, J. A., Schnider, J. T., Solari, M. G., Zheng, X. X. & Gorantla, V. S. Perspectives on the use of mesenchymal stem cells in vascularized composite allotransplantation. Front. Immunol. 4, 175 (2013).

  119. 119.

    Buron, F. et al. Human mesenchymal stem cells and immunosuppressive drug interactions in allogeneic responses: an in vitro study using human cells. Transplant. Proc. 41, 3347–3352 (2009).

  120. 120.

    Leonard, D. A. et al. Vascularized composite allograft tolerance across MHC barriers in a large animal model. Am. J. Transplant. 14, 343–355 (2014).

  121. 121.

    Kawai, T., Sachs, D. H., Sykes, M. & Cosimi, A. B. HLA-mismatched renal transplantation without maintenance immunosuppression. N. Engl. J. Med. 368, 1850–1852 (2013).

  122. 122.

    Scandling, J. D. et al. Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants. Am. J. Transplant. 12, 1133–1145 (2012).

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Dr. Stefan G. Tullius currently serves as an Einstein-BIH visiting fellow. This study was supported by the Einstein-BIH Visiting Fellow Program (to S.G.T., M.M. and I.M.S.) and the Biomedical Education Program (BMEP) of the German Academic Exchange Service (DAAD to J.I.).

Author information


  1. Division of Transplant Surgery, Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    • Jasper Iske
    • , Yeqi Nian
    • , Ryoichi Maenosono
    •  & Stefan G. Tullius
  2. Institute of Transplant Immunology, Integrated Research and Treatment Center Transplantation, Hannover Medical School, Hannover, Lower Saxony, Germany

    • Jasper Iske
  3. Department of Surgery, Charité – Universitätsmedizin Berlin, Campus Charité Mitte and Virchow-Klinikum, Berlin, Germany

    • Max Maurer
    •  & Igor M. Sauer
  4. Einstein-BIH Visiting Fellow, Department of Surgery, Charité-Universitätsmedizin Berlin, Campus Charité Mitte and Virchow-Klinikumc, Berlin, Germany

    • Stefan G. Tullius


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