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Acquired immunologic tolerance: with particular reference to transplantation

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Abstract

The first unequivocally successful bone marrow cell transplantation in humans was recorded in 1968 by the University of Minnesota team of Robert A. Good (Gatti et al. Lancet 2: 1366–1369, 1968). This achievement was a direct extension of mouse models of acquired immunologic tolerance that were established 15 years earlier. In contrast, organ (i.e. kidney) transplantation was accomplished precociously in humans (in 1959) before demonstrating its feasibility in any experimental model and in the absence of a defensible immunologic rationale. Due to the striking differences between the outcomes with the two kinds of procedure, the mechanisms of organ engraftment were long thought to differ from the leukocyte chimerism-associated ones of bone marrow transplantation. This and other concepts of alloengraftment and acquired tolerance have changed over time. Current concepts and their clinical implications can be understood and discussed best from the perspective provided by the life and times of Bob Good.

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References

  1. Billingham RE, Brent L, Medawar PB. “Actively acquired tolerance” of foreign cells. Nature 1953;172:603–6

    Article  PubMed  CAS  Google Scholar 

  2. Billingham R, Brent L, Medawar P. Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance. Philos Trans R Soc Lond (Biol) 1956;239:357–412

    Article  Google Scholar 

  3. Main JM, Prehn RT. Successful skin homografts after the administration of high dosage X radiation and homologous bone marrow. J Natl Cancer Inst 1955;15:1023–9

    PubMed  CAS  Google Scholar 

  4. Starzl TE, Marchioro TL, Waddell WR. The reversal of rejection in human renal homografts with subsequent development of homograft tolerance. Surg Gynecol Obstet 1963;117:385–95

    PubMed  CAS  Google Scholar 

  5. Starzl TE, Murase N, Demetris AJ, Trucco M, Abu-Elmagd K, Gray EA, et al. Lessons of organ-induced tolerance learned from historical clinical experience. Transplantation 2004;77:926–9

    Article  PubMed  Google Scholar 

  6. Starzl TE, Lakkis FG. The unfinished legacy of liver transplantation: emphasis on immunology. Hepatology 2006;43:S151–63

    Article  PubMed  CAS  Google Scholar 

  7. Starzl TE. The saga of liver replacement, with particular reference to the reciprocal influence of liver and kidney transplantation (1955–1967). J Am Coll Surg 2002;195:587–610

    Article  PubMed  Google Scholar 

  8. Takatsuki M, Uemoto SH, Inomata Y, Egawa H, Kiuchi T, Fujita S, et al. Weaning of immunosuppression in living donor liver transplant recipients. Transplantation 2001;72:449–54

    Article  PubMed  CAS  Google Scholar 

  9. Starzl TE, Marchioro TL, Porter KA, Taylor PD, Faris TD, Herrmann TJ, et al. Factors determining short- and long-term survival after orthotopic liver homotransplantation in the dog. Surgery 1965;58:131–55

    PubMed  Google Scholar 

  10. Starzl TE, Marchioro TL, Porter KA, Iwasaki Y, Cerilli GJ. The use of heterologous antilymphoid agents in canine renal and liver homotransplantation and in human renal homotransplantation. Surg Gynecol Obstet 1967;124:301–18

    PubMed  CAS  Google Scholar 

  11. Cordier G, Garnier H, Clot JP, Camplez P, Gorin JP, Clot Ph, et al. La greffe de foie orthotopique chez le porc. Mem Acad Chir (Paris) 1966;92:799–807

    CAS  Google Scholar 

  12. Peacock JH, Terblanche J. Orthotopic homotransplantation of the liver in the pig. In: Read AE, editor. The liver. London: Butterworth; 1967. p. 333

    Google Scholar 

  13. Calne RY, White HJO, Yoffa DE, Maginn RR, Binns RM, Samuel JR, et al. Observations of orthotopic liver transplantation in the pig. Br Med J 1967;2:478–80

    PubMed  CAS  Google Scholar 

  14. Calne RY, Sells RA, Pena JR, Davis DR, Millard PR, Herbertson BM, et al. Induction of immunological tolerance by porcine liver allografts. Nature 1969;223:472–4

    Article  PubMed  CAS  Google Scholar 

  15. Starzl TE. Rejection in unmodified animals. In: Experience in hepatic transplantation. Philadelphia: Saunders; 1969. p. 184–92

  16. Kamada N, Brons G, Davies HS. Fully allogeneic liver grafting in rats induces a state of systemic nonreactivity to donor transplantation antigens. Transplantation 1980;29:429–31

    Article  PubMed  CAS  Google Scholar 

  17. Qian S, Demetris AJ, Murase N, Rao AS, Fung JJ, Starzl TE. Murine liver allograft transplantation: tolerance and donor cell chimerism. Hepatology 1994;19:916–24

    Article  PubMed  CAS  Google Scholar 

  18. Corry RJ, Winn HJ, Russell PS. Primary vascularized allografts of hearts in mice: the role of H-2D, H-2K, and non-H-2 antigens in rejection. Transplantation 1973;6:343–50

    Google Scholar 

  19. Starzl TE, Groth CG, Brettschneider L, Penn I, Fulginiti VA, Moon JB, et al. Orthotopic homotransplantation of the human liver. Ann Surg 1968;168:392–415

    Article  PubMed  CAS  Google Scholar 

  20. Barnard CN. What we have learned about heart transplants. J Thorac Cardiovasc Surg 1968;56:457–68

    CAS  Google Scholar 

  21. Gatti RA, Meuwissen HJ, Allen HD, Hong R, Good RA. Immunological reconstitution of sex-linked lymphopenic immunological deficiency. Lancet 1968; 2:1366–9

    Article  PubMed  CAS  Google Scholar 

  22. Starzl TE. History of clinical transplantation. World J Surg 2000;24:759–82

    Article  PubMed  CAS  Google Scholar 

  23. Murray JE, Merrill JP, Dammin GJ, Dealy JB Jr, Walter CW, Brooke MS, et al. Study of transplantation immunity after total body irradiation: clinical and experimental investigation. Surgery 1960;48:272–84

    PubMed  CAS  Google Scholar 

  24. Hamburger J, Vaysse J, Crosnier J, Auvert J, Lalanne CL, Hopper J Jr. Renal homotransplantation in man after radiation of the recipient. Am J Med 1962;32:854–71

    Google Scholar 

  25. Kuss R, Legrain M, Mathe G, Nedey R, Camey M. Homologous human kidney transplantation. Experience with six patients. Postgrad Med J 1962;38:528–31

    PubMed  CAS  Google Scholar 

  26. Murray JE, Merrill JP, Harrison JH, Wilson RE, Dammin GJ. Prolonged survival of human-kidney homografts by immunosuppressive drug therapy. New Engl J Med 1963;268:1315–23

    PubMed  CAS  Google Scholar 

  27. Starzl TE. Experience in renal transplantation. Philadelphia: W.B. Saunders Company; 1964. p. 1–383

    Google Scholar 

  28. Starzl TE, Porter KA, Iwasaki Y, Marchioro TL, Kashiwagi N. The use of antilymphocyte globulin in human renal homotransplantation. In: Wolstenholme GEW, O’Connor M, editors. Antilymphocytic serum. London: J and A Churchill Limited; 1967. p. 4–34

    Google Scholar 

  29. Calne RY, Rolles K, White DJG, Thiru S, Evans DB, McMaster P, et al. Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs; 32 kidneys, 2 pancreases, and 2 livers. Lancet 1979;2:1033–6

    Article  PubMed  CAS  Google Scholar 

  30. Starzl TE, Weil R III, Iwatsuki S, Klintmalm G, Schroter GPJ, Koep LJ, et al. The use of cyclosporin A and prednisone in cadaver kidney transplantation. Surg Gynecol Obstet 1980;151:17–26

    PubMed  CAS  Google Scholar 

  31. Starzl TE, Todo S, Fung J, Demetris AJ, Venkataramanan R, Jain A. FK 506 for human liver, kidney and pancreas transplantation. Lancet 1989;2:1000–4

    Article  PubMed  CAS  Google Scholar 

  32. Todo S, Fung JJ, Starzl TE, Tzakis A, Demetris AJ, Kormos R, et al. Liver, kidney, and thoracic organ transplantation under FK 506. Ann Surg 1990;212:295–305

    Article  PubMed  CAS  Google Scholar 

  33. Starzl TE, Klintmalm GBG, Porter KA, Iwatsuki S, Schroter GPJ. Liver transplantation with use of cyclosporin A and prednisone. N Engl J Med 1981;305:266–9

    PubMed  CAS  Google Scholar 

  34. Todo S, Fung JJ, Starzl TE, Tzakis A, Doyle H, Abu-Elmagd K, et al. Single center experience with primary orthotopic liver transplantation under FK506 immunosuppression. Ann Surg 1994;220:297–309

    Article  PubMed  CAS  Google Scholar 

  35. Mathe G, Amiel JL, Schwarzenberg L, Cattan A, Schneider M. Haematopoietic chimera in man after allogenic (homologous) bone-marrow transplantation. Brit Med J 1963;2:1633–5

    PubMed  CAS  Google Scholar 

  36. Bach FH. Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome. Lancet 1968;2:1364–6

    Article  PubMed  CAS  Google Scholar 

  37. Thomas ED. Allogeneic marrow grafting: a story of man and dog. In: Terasaki PI, editor. History of transplantation: thirty-five recollections. Los Angeles, CA: UCLA Tissue Typing Laboratory; 1991. p. 379–93

    Google Scholar 

  38. Beatty PG, Clift RA, Mickelson EM, Nisperos BB, Flournoy N, Martin PJ, et al. Marrow transplantation from related donors other than HLA-Identical siblings. New Eng. J. Med. 1985;313:765–71

    PubMed  CAS  Google Scholar 

  39. Stewart BL, Storer B, Storek J, Joachim Deeg H, Storb R, Hansen JA, et al Duration of immunosuppressive treatment for chronic graft-versus-host disease. Blood 2004;104:3501–6

    Article  PubMed  CAS  Google Scholar 

  40. Barker CF, Billingham RE. The role of afferent lymphatics in the rejection of skin homografts. J Exp Med 1968;128:197–221

    Article  PubMed  CAS  Google Scholar 

  41. Lakkis FG, Arakelov A, Konieczny BT, Inoue Y. Immunologic ignorance of vascularized organ transplants in the absence of secondary lymphoid tissue. Nature Med 2000;6:686–8

    Article  PubMed  CAS  Google Scholar 

  42. Karrer U, Althage A, Odermatt B, Roberts CW, Korsmeyer SJ, Miyawaki S, et al. On the key role of secondary lymphoid organs in antiviral immune responses studied in alymphoplastic (aly/aly) and spleenless (Hox11(-)/-) mutant mice. J Exp Med 1997;185:2157–70

    Article  PubMed  CAS  Google Scholar 

  43. Starzl TE. Late results and complications. In: Experience in hepatic transplantation. Philadelphia, PA: WB Saunders Company; 1969. p. 348–93

  44. Starzl TE. Efforts to mitigate or prevent rejection. In: Experience in hepatic transplantation. Philadelphia: Saunders, 1969. p. 227–33

  45. Doherty PC, Zinkernagel RM. A biological role for the major histocompatibility antigens. Lancet 1975;1(7922):1406–9

    Article  PubMed  CAS  Google Scholar 

  46. Zinkernagel RM, Doherty PC. The discovery of MHC restriction. Immunol Today 1997;18:14–7

    Article  PubMed  CAS  Google Scholar 

  47. Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 1973;137:1142–62

    Article  PubMed  CAS  Google Scholar 

  48. Webb S, Morris C, Sprent J. Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell 1990;63:1249–56

    Article  PubMed  CAS  Google Scholar 

  49. Moskophidis D, Lechner F, Pircher H, Zinkernagel RM. Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells. Nature 1993;362:758–61

    Article  PubMed  CAS  Google Scholar 

  50. Wilson WEC, Kirkpatrick CH. Immunologic aspects of renal homotransplantations. In: Starzl TE, editor. Experience in renal transplantation. Philadelphia: W.B. Saunders Company; 1964. p. 239–61

    Google Scholar 

  51. Kirkpatrick CH, Wilson WEC, Talmage DW. Immunologic studies in human organ transplantation. I. Observations and characterization of suppressed cutaneous reactivity in uremia. J Exp Med 1964;119:727

    Article  PubMed  CAS  Google Scholar 

  52. Starzl TE, Demetris AJ, Trucco M, Murase N, Ricordi C, Ildstad S, et al. Cell migration and chimerism after whole-organ transplantation: the basis of graft acceptance. Hepatology 1993;17:1127–52

    Article  PubMed  CAS  Google Scholar 

  53. Kashiwagi N, Porter KA, Penn I, Brettschneider L, Starzl TE. Studies of homograft sex and of gamma globulin phenotypes after orthotopic homotransplantation of the human liver. Surg Forum 1969;20:374–6

    PubMed  CAS  Google Scholar 

  54. Murase N, Demetris AJ, Matsuzaki T, Yagihasi A, Todo S, Fung J, et al. Long survival in rats after multivisceral versus isolated small bowel allotransplantation under FK 506. Surgery 1991;110:87–98

    PubMed  CAS  Google Scholar 

  55. Iwaki Y, Starzl TE, Yagihashi A, Taniwaki S, Abu-Elmagd K, Tzakis A, et al. Replacement of donor lymphoid tissue in human small bowel transplants under FK 506 immunosuppression. Lancet 1991;337:818–9

    Article  PubMed  CAS  Google Scholar 

  56. Nemlander A, Soots A, von Willebrand E, Husberg B, Hayry P. Redistribution of renal allograft-responding leukocytes during rejection. II. Kinetics and specificity. J Exp Med 1982;156:1087–100

    Article  PubMed  CAS  Google Scholar 

  57. Larsen CP, Morris PJ, Austyn JM. Migration of dendritic leukocytes from cardiac allografts into host spleens. A novel route for initiation of rejection. J Exp Med 1990;171:307–14

    Article  PubMed  CAS  Google Scholar 

  58. Demetris AJ, Qian S, Sun H, Fung JJ, Yagihashi A, Murase N, et al. Early events in liver allograft rejection: delineation of sites simultaneous intragraft and recipient lymphoid tissue sensitization. Am J Pathol 1991;138:609–18

    PubMed  CAS  Google Scholar 

  59. Starzl TE, Todo S, Tzakis A, Alessiani M, Casavilla A, Abu-Elmagd K, et al. The many faces of multivisceral transplantation. Surg Gynecol Obstet 1991;172:335–44

    PubMed  CAS  Google Scholar 

  60. Murase N, Demetris AJ, Woo J, Tanabe M, Furuya T, Todo S, et al. Graft versus host disease (GVHD) after BN to LEW compared to LEW to BN rat intestinal transplantation under FK 506. Transplantation 1993;55:1–7

    PubMed  CAS  Google Scholar 

  61. Starzl TE, Demetris AJ, Murase N, Ildstad S, Ricordi C, Trucco M. Cell migration, chimerism, and graft acceptance. Lancet 1992;339:1579–82

    Article  PubMed  CAS  Google Scholar 

  62. Starzl TE, Demetris AJ, Trucco M, Ramos H, Zeevi A, Rudert WA, et al. Systemic chimerism in human female recipients of male livers. Lancet 1992;340:876–7

    Article  PubMed  CAS  Google Scholar 

  63. Starzl TE, Demetris AJ, Trucco M, Ricordi C, Ildstad S, Terasaki PI, et al. Chimerism after liver transplantation for type IV glycogen storage disease and Type I Gaucher’s disease. N Engl J Med 1993;328:745–9

    Article  PubMed  CAS  Google Scholar 

  64. Starzl TE, Demetris AJ, Trucco M, Zeevi A, Ramos H, Terasaki P, et al. Chimerism and donor-specific nonreactivity 27 to 29 years after kidney allotransplantation. Transplantation 1993;55:1272–7

    Article  PubMed  CAS  Google Scholar 

  65. Przepiorka D, Thomas ED, Durham DM, Fisher L. Use of a probe to repeat sequence of the Y chromosome for detection of host cells in peripheral blood of bone marrow transplant recipients. Am J Clin Pathol 1991;95:201–6

    PubMed  CAS  Google Scholar 

  66. Starzl TE, Demetris AJ. Transplantation milestones: viewed with one- and two-way paradigms of tolerance. JAMA 1995;273:876–9

    Article  PubMed  CAS  Google Scholar 

  67. Starzl TE, Zinkernagel R. Antigen localization and migration in immunity and tolerance. New Engl J Med 1998;339:1905–13

    Article  PubMed  CAS  Google Scholar 

  68. Owen RD. Immunogenetic consequences of vascular anastomoses between bovine twins. Science 1945;102:400–1

    Article  PubMed  Google Scholar 

  69. Martinez C, Shapiro F, Good RA. Essential duration of parabiosis and development of tolerance to skin homografts in mice. Proc Soc Exp Biol Med 1960;104:256–9

    PubMed  CAS  Google Scholar 

  70. Starzl TE, Demetris AJ, Murase N, Trucco M, Thomson AW, Rao AS. The lost chord: Microchimerism. Immunol Today 1996;17:577–84

    Article  PubMed  CAS  Google Scholar 

  71. Starzl TE. The mystique of organ transplantation. J Am Coll Surg 2005;201:160–70

    Article  PubMed  Google Scholar 

  72. Starzl TE. Chimerism and tolerance in transplantation. Proc Natl Acad Sci 2004;101(Suppl. 2):14607–14

    Article  PubMed  CAS  Google Scholar 

  73. Demetris AJ, Murase N, Fujisaki S, Fung JJ, Rao AS, Starzl TE. Hematolymphoid cell trafficking, microchimerism, and GVH reactions after liver, bone marrow, and heart transplantation. Transplant Proc 1993;25:3337–44

    PubMed  CAS  Google Scholar 

  74. Murase N, Demetris AJ, Woo J, Tanabe M, Furuya T, Todo S, et al Graft versus host disease (GVHD) after BN to LEW compared to LEW to BN rat intestinal transplantation under FK 506. Transplantation 1993;55:1–7

    PubMed  CAS  Google Scholar 

  75. Terakura M, Murase N, Demetris AJ, Ye Q, Thomson A, Starzl TE. Lymphoid/non-lymphoid compartmentalization of donor leukocyte chimerism in rat recipients of heart allografts, with or without adjunct bone marrow. Transplantation 1998;66:350–7

    Article  PubMed  CAS  Google Scholar 

  76. Sakamoto T, Ye Q, Lu L, Demetris AJ, Starzl TE, Murase N. Donor hematopoietic progenitor cells in non myeloablated rat recipients of allogeneic bone marrow and liver grafts. Transplantation 1999;67:833–840

    Article  PubMed  CAS  Google Scholar 

  77. Lu L, Rudert WA, Qian S, McCaslin D, Fu F, Rao AS, et al. Growth of donor-derived dendritic cells from the bone marrow of murine liver allograft recipients in response to granulocyte/macrophage colony-stimulating factor. J Exp Med 1995;182:379–87

    Article  PubMed  CAS  Google Scholar 

  78. Ricordi C, Ildstad ST, Demetris AJ, Abou El-Ezz AY, Murase N, Starzl TE. Donor dendritic cells repopulaton in recipients after rat-to-mouse bone-marrow transplantation. Lancet 1992;339:1610–11

    Article  PubMed  CAS  Google Scholar 

  79. Zinkernagel RM, Moskophidis D, Kundig T, Oehen S, Pircher H, Hengartner H. Effector T-cell induction and T-cell memory versus peripheral deletion of T cells. Immunol Rev 1993;131:199–223

    Article  Google Scholar 

  80. Zinkernagel RM, Hengartner H. T-cell mediated immunopathology versus direct cytolysis by virus: implications for HIV and AIDS. Immunol Today 1994;15: 262–8

    Article  PubMed  CAS  Google Scholar 

  81. Zinkernagel RM. Immunology taught by viruses. Science 1996;271:173–8

    Article  PubMed  CAS  Google Scholar 

  82. Zinkernagel RM, Ehl S, Aichele P, Oehen S, Kundig T, Hengartner H. Antigen localization regulates immune responses in a dose- and time-dependent fashion: a geographical view of immune reactivity. Immunol Reviews 1997;156:199–209

    Article  CAS  Google Scholar 

  83. Sivasai KS, Alevy TY, Duffy BF, Brennan DC, Singer GG, Shenoy S, et al. Peripheral blood microchimerism in human liver and renal transplant recipients: rejection despite donor-specific chimerism. Transplantation 1997;64:427–32

    Article  PubMed  CAS  Google Scholar 

  84. Inman B, Halloran B, Melk A, Ramassar V, Halloran PF. Microchimerism in sensitized renal patients. Transplantation 1999;67:1381–4

    Article  PubMed  CAS  Google Scholar 

  85. Lafferty KJ, Prowse SJ, Simeonovic CJ. Immunobiology of tissue transplantation: a return to the passenger leukocyte concept. Ann Rev Immunol 1983;1:143–73

    Article  CAS  Google Scholar 

  86. Algire GH, Weaver JM, Prehn RT. Studies on tissue homotransplantation in mice using diffusion chamber methods. Ann New York Acad Sci 1957;64:1009

    Article  CAS  Google Scholar 

  87. Kiyomoto T, Toyokawa H, Nakao A, Kaizu T, Okuda T, Demetris AJ, et al. The difficulty of eliminating donor leukocyte microchimerism in rat recipients bearing established organ allografts. Transplantation 2006;81:438–44

    Article  PubMed  Google Scholar 

  88. Starzl TE, Zinkernagel R. Transplantation tolerance from a historical perspective. Nat Rev: Immunol 2001;1:233–9

    Article  CAS  Google Scholar 

  89. Bonilla WV, Geuking MB, Aichele P, Ludewig B, Hengartner H, Zinkernagel RM. Microchimerism maintains deletion of the donor cell-specific CD8+ T cell repertoire. J Clin Invest 2006;116:156–62

    Article  PubMed  CAS  Google Scholar 

  90. Penn I, Hammond W, Brettschneider L, Starzl TE. Malignant lymphomas in transplantation patients. Transplant Proc 1969;1:106–12

    PubMed  CAS  Google Scholar 

  91. Starzl TE, Penn I, Putnam CW, Groth CG, Halgrimson CG. Iatrogenic alterations of immunologic surveillance in man and their influence on malignancy. Transplant Rev 1971;7:112–45

    PubMed  CAS  Google Scholar 

  92. Barber WH, Mankin JA, Laskow DA, Dierhoi MH, Julian BA, Curtis JJ, et al. Long term results of a controlled prospective study with transfusion of donor-specific bone marrow in 57 cadaveric renal allograft recipients. Transplantation 1991;51:70–5

    Article  PubMed  CAS  Google Scholar 

  93. Fontes P, Rao A, Demetris AJ, Zeevi A, Trucco M, Carroll P, et al. Augmentation with bone marrow of donor leukocyte migration for kidney, liver, heart, and pancreas islet transplantation. Lancet 1994;344:151–5

    Article  PubMed  CAS  Google Scholar 

  94. Tryphonopoulos P, Tzakis AG, Weppler D, Garcia-Morales R, Kato T, Madariaga JR, et al. The role of donor bone marrow infusions in withdrawal of Immunosuppression in adult liver allotransplantation. Am J Transplant 2005;5:608–13

    Article  PubMed  Google Scholar 

  95. Murase N, Starzl TE, Tanabe M, Fujisaki S, Miyazawa H, Ye Q, et al. Variable chimerism, graft-versus-host disease, and tolerance after different kinds of cell and whole organ transplantation from Lewis to brown Norway rats. Transplantation 1995;60:158–71

    PubMed  CAS  Google Scholar 

  96. Starzl TE, Murase N, Abu-Elmagd K, Gray EA, Shapiro R, Eghtesad B, et al. Tolerogenic immunosuppression for organ transplantation. Lancet 2003;361:1502–10

    Article  PubMed  Google Scholar 

  97. Reyes J, Mazariegos GV, Abu-Elmagd K, Macedo C, Bond GJ, Murase N, et al. Intestinal transplantation under tacrolimus monotherapy after perioperative lymphoid depletion with rabbit anti-thymocyte globulin (ThymoglobulinR). Am J Transplant 2005;5:1430–6

    Article  PubMed  CAS  Google Scholar 

  98. McCurry K, Iacano A, Zeevi A, Yousem S, Girnita A, Husain S, et al. Early outcomes in human lung transplantation with Thymoglobulin or Campath-1H for recipient pretreatment followed by post-transplant tacrolimus near-monotherapy. J Thorac Cardiovasc Surg 2005;130:528–37

    Article  PubMed  Google Scholar 

  99. Shapiro R, Ellis D, Tan HP, Moritz ML, Basu A, Vats AN, et al. Antilymphoid antibody preconditioning with tacrolimus monotherapy for pediatric renal transplantation. J Pediatr 2006;148:813–8

    Article  PubMed  CAS  Google Scholar 

  100. Shapiro R, Basu A, Tan H, Gray E, Kahn A, Randhawa P, et al. Kidney transplantation under minimal immunosuppression after pretransplant lymphoid depletion with thymoglobulin or campath. J Am Coll Surg 2005;200:505–15

    Article  PubMed  Google Scholar 

  101. Lilly JR, Giles G, Hurwitz R, Schroter G, Takagi H, Gray S, et al. Renal homotransplantation in pediatric patients. Pediatr 1971;47:548–57

    CAS  Google Scholar 

  102. Eghtesad B, Fung JJ, Demetris AJ, Murase N, Ness R, Bass DC, et al. Mechanism-based principles of immunosuppression for liver transplantation in HCV-infected patients. Liver Transplant 2005;11:1343–52

    Article  Google Scholar 

  103. Starzl TE. Organ transplantation: a practical triumph and epistemologic collapse. Proc Am Philos Soc 2003;147:226–45

    PubMed  Google Scholar 

  104. Kirk AD, Hale DA, Mannon RB, Kleiner DE, Hoffmann SC, Kampen RL, et al. Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Transplantation 2003;76:120–9

    Article  PubMed  CAS  Google Scholar 

  105. Knechtle SJ, Pirsch JD, Fechner HJ Jr, Becker BN, Friedl A, Colvin RB, et al. Campath-1H induction plus rapamycin monotherapy for renal transplantation: results of a pilot study. Am J Transplant 2003;3:722–30

    Article  PubMed  CAS  Google Scholar 

  106. Perico N, Amuchastegui S, Bontempelli M, Remuzzi G. The kidney triggers graft-versus-host disease in experimental combined transplantation of kidney and stem cell-enriched peripheral leukocytes. J Am Soc Nephrol 1996;7:2254–8

    PubMed  CAS  Google Scholar 

  107. Ricordi C, Tzakis AG, Zeevi A, Rybka WB, Demetris AJ, Fontes PAC, et al. Reversal of graft-versus-host disease with infusion of autologous bone marrow. Cell Transplantation 1994;3:187–92

    PubMed  CAS  Google Scholar 

  108. Wood K, Sachs DH. Chimerism and transplantation tolerance: cause and effect. Immunol Today 1996;17(12):584–588

    Article  PubMed  CAS  Google Scholar 

  109. Wekerle T, Sykes M. Mixed chimerism as an approach for the induction of transplantation tolerance. Transplantation 1999;68:459–467

    Article  PubMed  CAS  Google Scholar 

  110. Bushell A, Pearson TC, Morris PJ, Wood KJ. Donor-recipient microchimerism and tolerance induction. Transplantation 1996;61:170–2

    Article  Google Scholar 

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  1. Transplantation Institute, University of Pittsburgh Medical Center (UPMC), 7th Floor, South, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA

    Thomas E. Starzl

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Correspondence to Thomas E. Starzl.

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Presented at the First Robert A Good Society Symposium, St. Petersburg, FL, 2006.

Keynote Address: Inaugural meeting of the Robert A. Good Immunology Society, June 9–11, 2006, Tampa, Florida.

This work was supported by National Institutes of Health Grant RO1 DK64207, and unrestricted gifts from Mr. Robert Eberly and Frank and Athena Sarris.

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Starzl, T.E. Acquired immunologic tolerance: with particular reference to transplantation. Immunol Res 38, 6–41 (2007). https://doi.org/10.1007/s12026-007-0001-7

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