• 1
    Ildstad ST, Sachs DH. Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of allografts or xenografts. Nature 1984; 307: 168170.
  • 2
    Zinkernagel RM. Thymus function and reconstitution of immunodeficiency. N Engl J Med 1978; 298: 222.
  • 3
    Zinkernagel RM, Althage A, Waterfield E et al. Restriction specificities, alloreactivity, and allotolerance expressed by T cells from nude mice reconstituted with H-2-compatible or -incompatible thymus grafts. J Exp Med 1980; 151: 376399.
  • 4
    Sykes M. Mixed chimerism and transplant tolerance. Immunity 2001; 14: 417424.
  • 5
    Sharabi Y, Sachs DH. Engraftment of allogeneic bone marrow following administration of anti-T cell monoclonal antibodies and low-dose irradiation. Transplant Proc 1989; 21: 233235.
  • 6
    Wekerle T, Sayegh MH, Hill J et al. Extrathymic T cell deletion and allogeneic stem cell engraftment induced with costimulatory blockade is followed by central T cell tolerance. J Exp Med 1998; 187: 20372044.
  • 7
    Adams AB, Durham MM, Kean L et al. Costimulation blockade, busulfan, and bone marrow promote titratable macrochimerism, induce transplantation tolerance, and correct genetic hemoglobinopathies with minimal myelosuppression. J Immunol 2001; 167: 11031111.
  • 8
    Wekerle T, Sykes M. Mixed chimerism as an approach for the induction of transplantation tolerance. Transplantation 1999; 68: 459467.
  • 9
    Wekerle T, Sachs DH, Sykes M. Mixed chimerism for the induction of tolerance: potential applicability in clinical composite tissue grafting. Transplant Proc 1998; 30: 27082710.
  • 10
    Tomita Y, Khan A, Sykes M. Role of intrathymic clonal deletion and peripheral anergy in transplantation tolerance induced by bone marrow transplantation in mice conditioned with a nonmyeloablative regimen. J Immunol 1994; 153: 10871098.
  • 11
    Durham MM, Bingaman AW, Adams AB et al. Cutting edge: administration of anti-CD40 ligand and donor bone marrow leads to hemopoietic chimerism and donor-specific tolerance without cytoreductive conditioning. J Immunol 2000; 165: 14.
  • 12
    Kawai T, Sogawa H, Koulmanda M et al. Long-term islet allograft function in the absence of chronic immunosuppression: a case report of a nonhuman primate previously made tolerant to a renal allograft from the same donor. Transplantation 2001; 72: 351354.
  • 13
    Kawai T, Cosimi AB, Colvin RB et al. Mixed allogeneic chimerism and renal allograft tolerance in cynomolgus monkeys. Transplantation 1995; 59: 256262.
  • 14
    Kimikawa M, Kawai T, Sachs DH, Colvin RB, Bartholomew A, Cosimi AB. Mixed chimerism and transplantation tolerance induced by a nonlethal preparative regimen in cynomolgus monkeys. Transplant Proc 1997; 29: 1218.
  • 15
    Kawai T, Poncelet A, Sachs DH et al. Long-term outcome and alloantibody production in a non-myeloablative regimen for induction of renal allograft tolerance. Transplantation 1999; 68: 17671775.
  • 16
    Kawai T, Abrahamian G, Sogawa H et al. Costimulatory blockade for induction of mixed chimerism and renal allograft tolerance in nonhuman primates. Transplant Proc 2001; 33: 221222.
  • 17
    Kawai T, Sogawa H, Boskovic S et al. CD154 blockade for induction of mixed chimerism and prolonged renal allograft survival in nonhuman primates. Am J Transplant 2004; 4: 13911398.
  • 18
    Kimikawa M, Sachs DH, Colvin RB, Bartholomew A, Kawai T, Cosimi AB. Modifications of the conditioning regimen for achieving mixed chimerism and donor-specific tolerance in cynomolgus monkeys. Transplantation 1997; 64: 709716.
  • 19
    Sayegh MH, Fine NA, Smith JL, Rennke HG, Milford EL, Tilney NL. Immunologic tolerance to renal allografts after bone marrow transplants from the same donors. Ann Intern Med 1991; 114: 954955.
  • 20
    Buhler LH, Spitzer TR, Sykes M et al. Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease. Transplantation 2002; 74: 14051409.
  • 21
    Fudaba Y, Spitzer TR, Shaffer J et al. Myeloma responses and tolerance following combined kidney and nonmyeloablative marrow transplantation: In vivo and in vitro analyses. Am J Transplant 2006; 6:21212133.
  • 22
    Spitzer TR, Delmonico F, Tolkoff-Rubin N et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: the induction of allograft tolerance through mixed lymphohematopoietic chimerism. Transplantation 1999; 68: 480484.
  • 23
    Kean LS, Durham MM, Adams AB et al. A cure for murine sickle cell disease through stable mixed chimerism and tolerance induction after nonmyeloablative conditioning and major histocompatibility complex-mismatched bone marrow transplantation. Blood 2002; 99: 18401849.
  • 24
    Kean LS, Manci EA, Perry J et al. Chimerism and cure: hematologic and pathologic correction of murine sickle cell disease. Blood 2003; 102: 45824593.
  • 25
    Iannone R, Luznik L, Engstrom LW et al. Effects of mixed hematopoietic chimerism in a mouse model of bone marrow transplantation for sickle cell anemia. Blood 2001; 97: 39603965.
  • 26
    Horan JT, Liesveld JL, Fenton P, Blumberg N, Walters MC. Hematopoietic stem cell transplantation for multiply transfused patients with sickle cell disease and thalassemia after low-dose total body irradiation, fludarabine, and rabbit anti-thymocyte globulin. Bone Marrow Transplant 2005; 35: 171177.
  • 27
    Watkins DI. The evolution of major histocompatibility class I genes in primates. Crit Rev Immunol 1995; 15: 129.
  • 28
    Knapp LA, Lehmann E, Piekarczyk MS, Urvater JA, Watkins DI. A high frequency of Mamu-A*01 in the rhesus macaque detected by polymerase chain reaction with sequence-specific primers and direct sequencing. Tissue Antigens 1997; 50: 657661.
  • 29
    Lobashevsky A, Smith JP, Kasten-Jolly J et al. Identification of DRB alleles in rhesus monkeys using polymerase chain reaction-sequence-specific primers (PCR-SSP) amplification. Tissue Antigens 1999; 54: 254263.
  • 30
    Healy DL, Bacher J, Hodgen GD. A method of thymectomy in macaques. J Med Primatol 1983; 12: 89100.
  • 31
    Lebreton L, Jost E, Carboni B et al. Structure-immunosuppressive activity relationships of new analogues of 15-deoxyspergualin 2. Structural modifications of the spermidine moiety. J Med Chem 1999; 42: 47494763.
  • 32
    Adams AB, Williams MA, Jones TR et al. Heterologous immunity provides a potent barrier to transplantation tolerance [see comment]. J Clin Inves 2003; 111: 18871895.
  • 33
    Vogel TU, Evans DT, Urvater JA, O'Connor DH, Hughes AL, Watkins DI. Major histocompatibility complex class I genes in primates: co-evolution with pathogens. Immunol Rev 1999; 167: 327337.
  • 34
    Otting N, Heijmans CM, Noort RC et al. Unparalleled complexity of the MHC class I region in rhesus macaques. Proc Natl Acad Sci USA 2005; 102: 16261631.
  • 35
    Lobashevsky AL, Thomas JM. Six mamu-A locus alleles defined by a polymerase chain reaction sequence specific primer method. Hum Immunol 2000; 61: 10131020.
  • 36
    Han D, Ricordi C, Xu X, Kenyon NS. Quantitative polymerase chain reaction assessment of chimerism in non-human primates after sex-mismatched islet and bone marrow transplantation. Transplantation 2000; 69: 17171721.
  • 37
    Panse JP, Heimfeld S, Guthrie KA et al. Allogeneic peripheral blood stem cell graft composition affects early T-cell chimaerism and later clinical outcomes after non-myeloablative conditioning. Br J Haematol 2005; 128: 659667.
  • 38
    Baron F, Storb R. Allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning as treatment for hematologic malignancies and inherited blood disorders. Mol Ther 2006; 13: 2641.
  • 39
    Maris M, Storb R. The transplantation of hematopoietic stem cells after non-myeloablative conditioning: a cellular therapeutic approach to hematologic and genetic diseases. Immunol Res 2003; 28: 1324.
  • 40
    Storb R. Non-myeloablative allogeneic transplantation—State-of-the-art. Pediatr Transplant 2004; 8(Suppl. 5): 1218.
  • 41
    Kimikawa M, Kawai T, Sachs DH, Colvin RB, Bartholomew A, Cosimi AB. Mixed chimerism and transplantation tolerance induced by a nonlethal preparative regimen in cynomolgus monkeys. Transplant Proc 1997; 29: 1218.
  • 42
    Trambley J, Bingaman AW, Lin A et al. Asialo GM1(+) CD8(+) T cells play a critical role in costimulation blockade-resistant allograft rejection. J Clin Inves 1999; 104: 17151722.
  • 43
    Markees TG, Phillips NE, Gordon EJ et al. Long-term survival of skin allografts induced by donor splenocytes and anti-CD154 antibody in thymectomized mice requires CD4(+) T cells, interferon-gamma, and CTLA4. J Clin Invest 1998; 101: 24462455.
  • 44
    Xu H, Montgomery SP, Preston EH et al. Studies investigating pretransplant donor-specific blood transfusion, sirolimus, and the CD154-specific antibody IDEC-131 in a nonhuman primate model of skin allotransplantation. J Immunol 2003; 170: 27762782.
  • 45
    Preston EH, Xu H, Dhanireddy KK et al. IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates. Am J Transplant 2005; 5: 10321041.
  • 46
    Thomas JM, Contreras JL, Smyth CA et al. Successful reversal of streptozotocin-induced diabetes with stable allogeneic islet function in a preclinical model of type 1 diabetes. Diabetes 2001; 50: 12271236.
  • 47
    Thomas JM, Contreras JL, Jiang XL et al. Peritransplant tolerance induction in macaques: early events reflecting the unique synergy between immunotoxin and deoxyspergualin. Transplantation 1999; 68: 16601673.
  • 48
    Thomas JM, Eckhoff DE, Contreras JL et al. Durable donor-specific T and B cell tolerance in rhesus macaques induced with peritransplantation anti-CD3 immunotoxin and deoxyspergualin: absence of chronic allograft nephropathy. Transplantation 2000; 69: 24972503.
  • 49
    Contreras JL, Wang PX, Eckhoff DE et al. Peritransplant tolerance induction with anti-CD3-immunotoxin: a matter of proinflammatory cytokine control. Transplantation 1998; 65: 11591169.
  • 50
    Hutchings A, Wu J, Asiedu C et al. The immune decision toward allograft tolerance in non-human primates requires early inhibition of innate immunity and induction of immune regulation. Transpl Immunol 2003; 11: 335344.
  • 51
    Zhou D, O'Brien C, Shum J et al. LF 15-0195, a novel immunosuppressive agent prevents rejection and induces operational tolerance in a mouse cardiac allograft model. Transplantation 2003; 76: 644650.
  • 52
    Min WP, Zhou D, Ichim TE et al. Synergistic tolerance induced by LF15-0195 and anti-CD45RB monoclonal antibody through suppressive dendritic cells. Transplantation 2003; 75: 11601165.
  • 53
    Larsen CP, Elwood ET, Alexander DZ et al. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 1996; 381: 434438.
  • 54
    Pearson TC, Alexander DZ, Corbascio M et al. Analysis of the B7 costimulatory pathway in allograft rejection. Transplantation 1997; 63: 14631469.
  • 55
    Sachs DH. Mixed chimerism as an approach to transplantation tolerance. Clin Immunol 2000; 95: S63—S68.
  • 56
    Sykes M, Ohdan H, Manilay JO, Wekerle T, Yang YG. Hematopoietic chimerism and tolerance of T cells, B cells, and NK cells. Transplant Proc 1998; 30: 4020.
  • 57
    Sykes M, Sachs DH. Mixed allogeneic chimerism as an approach to transplantation tolerance [erratum appears in Immunol Today 1988; 9(5): 131]. Immunol Today 1988; 9: 2327.
  • 58
    Sykes M, Spitzer TR. Non-myeloblative induction of mixed hematopoietic chimerism: application to transplantation tolerance and hematologic malignancies in experimental and clinical studies. Cancer Treat Res 2002; 110: 7999.
  • 59
    Sayegh MH, Carpenter CB. Transplantation 50 years later–progress, challenges, and promises. N Engl J Med 2004; 351: 27612766.
  • 60
    Platt OS, Guinan EC. Bone marrow transplantation in sickle cell anemia—The dilemma of choice. N Engl J Med 1996; 335: 426428.
  • 61
    Vermylen C, Cornu G, Ferster A et al. Haematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium. Bone Marrow Transplant 1998; 22: 16.
  • 62
    Walters MC. Bone marrow transplantation for sickle cell disease: where do we go from here? J Pediatr Hematol Oncol 1999; 21: 467474.
  • 63
    Walters MC, Patience M, Leisenring W et al. Barriers to bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant 1996; 2: 100104.
  • 64
    Walters MC, Patience M, Leisenring W et al. Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant 2001; 7: 665673.
  • 65
    Buhlmann JE, Gonzalez M, Ginther B et al. Cutting edge: sustained expansion of CD8+ T cells requires CD154 expression by Th cells in acute graft versus host disease. J Immunol 1999; 162: 43734376.
  • 66
    Blazar BR, Taylor PA, Boyer MW, Panoskaltsis-Mortari A, Allison JP, Vallera DA. CD28/B7 interactions are required for sustaining the graft-versus-leukemia effect of delayed post-bone marrow transplantation splenocyte infusion in murine recipients of myeloid or lymphoid leukemia cells. J Immunol 1997; 159: 34603473.
  • 67
    Adams AB, Pearson TC, Larsen CP. Conventional immunosuppression and co-stimulation blockade. Philos Trans R Soc Lond B Biol Sci 2001; 356: 703705.
  • 68
    Adams AB, Shirasugi N, Durham MM et al. Calcineurin inhibitor-free CD28 blockade-based protocol protects allogeneic islets in nonhuman primates. Diabetes 2002; 51: 265270.
  • 69
    Sykes M, Szot GL, Swenson KA, Pearson DA. Induction of high levels of allogeneic hematopoietic reconstitution and donor-specific tolerance without myelosuppressive conditioning. Nat Med 1997; 3: 783787.
  • 70
    Wekerle T, Kurtz J, Ito H et al. Allogeneic bone marrow transplantation with co-stimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment. Nat Med 2000; 6: 464469.
  • 71
    Wekerle T, Nikolic B, Pearson DA, Swenson KG, Sykes M. Minimal conditioning required in a murine model of T cell depletion, thymic irradiation and high-dose bone marrow transplantation for the induction of mixed chimerism and tolerance. Transpl Int 2002; 15: 248253.
  • 72
    Field EH, Strober S. Tolerance, mixed chimerism and protection against graft-versus-host disease after total lymphoid irradiation. Philos Trans R Soc Lond B Biol Sci 2001; 356: 739748.
  • 73
    Hubbard WJ, Moore JK, Contreras JL et al. Phenotypic and functional analysis of T-cell recovery after anti-CD3 immunotoxin treatment for tolerance induction in rhesus macaques. Hum Immunol 2001; 62: 479487.
  • 74
    Thomas JM, Hubbard WJ, Sooudi SK, Thomas FT. STEALTH matters: a novel paradigm of durable primate allograft tolerance. Immunol Rev 2001; 183: 223233.
  • 75
    Kirk AD, Mannon RB, Kleiner DE et al. Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin. Transplantation 2005; 80: 10511059.
  • 76
    Koehn B, Gangappa S, Miller JD, Ahmed R, Larsen CP. Patients, pathogens, and protective immunity: the relevance of virus-induced alloreactivity in transplantation. J Immunol 2006; 176: 26912696.
  • 77
    Williams MA, Adams AB, Walsh MB et al. Primary and secondary immunocompetence in mixed allogeneic chimeras. J Immunol 2003; 170: 23822389.
  • 78
    Williams MA, Onami TM, Adams AB et al. Cutting edge: persistent viral infection prevents tolerance induction and escapes immune control following CD28/CD40 blockade-based regimen. J Immunol 2002; 169: 53875391.
  • 79
    Ely LK, Green KJ, Beddoe T et al. Antagonism of antiviral and allogeneic activity of a human public CTL clonotype by a single altered peptide ligand: implications for allograft rejection. J Immunol 2005; 174: 55935601.
  • 80
    Forman D, Welsh RM, Markees TG et al. Viral abrogation of stem cell transplantation tolerance causes graft rejection and host death by different mechanisms. J Immunol 2002; 168: 60476056.