Tolerogenic dendritic cells and negative vaccination in transplantation: From rodents to clinical trials

Frontiers in Immunology

Volumn 3, Issue AUG, 2012, Pages

  Moreau, Aurélie ^a   Varey, Emilie ^a   Bériou, Gaëlle ^a   Hill, Marcelo ^a   Bouchet Delbos, Laurence ^a   Segovia, Mercedes ^a   Cuturi, Maria Cristina ^a  

^a HÔTEL DIEU   (France)

Author keywords

Clinical trial; Immune tolerance; Tolerogenic dendritic cells; Translational research; Transplantation

Indexed keywords

EID: 84871669007     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2012.00218     Document Type: Article

References (85)

1. Allan, R. S., Waithman, J., Bedoui, S., Jones, C. M., Villadangos, J. A., Zhan, Y., Lew, A. M., Shortman, K., Heath, W. R., and Carbone, E R. (2006) Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity 25: 153-162.
2. Ashton-Chess, J., and Blancho, G. (2005) An in vitro evaluation of the potential suitability of peripheral blood CD14(+) and bone marrow CD34(+)-derived dendritic cells for a tolerance inducing regimen in the primate. J. Immunol. Methods 297: 237-252.
3. Asiedu, C., Dong, S. S., Pereboev, A., Wang, W., Navarro, J., Curiel, D. T., and Thomas, J. M. (2002) Rhesus monocyte-derived dendritic cells modified to over-express TGF-beta1 exhibit potent veto activity. Transplantation 74: 629-637.
4. Barratt-Boyes, S. M., Zimmer, M. I., Harshyne, L. A., Meyer, E. M., Watkins, S. C., Capuano, S. 3rd, Murphey-Corb, M., Falo, L. D. Jr., and Donnenberg, A. D. (2000) Maturation and trafficking of monocyte-derived dendritic cells in monkeys: implications for dendritic cell-based vaccines. J. Immunol. 164: 2487-2495.
5. Berger, T. G., Schulze-Koops, H., Schafer, M., Muller, E., and Lutz, M. B. (2009) Immature and maturation-resistant human dendritic cells generated from bone marrow require two stimulations to induce T cell anergy in vitro. PLoS ONE 4: e6645. doi: 10.1371/journal.pone.0006645
6. Berger, T. G., Strasser, E., Smith, R., Carste, C., Schuler-Thurner, B., Kaempgen, E., and Schuler, G. (2005) Efficient elutriation of monocytes within a closed system (Elutra) for clinical-scale generation of dendritic cells. J. Immunol. Methods 298: 61-72.
7. Beriou, G., Peche, H., Guillonneau, C., Merieau, E., and Cuturi, M. C. (2005) Donor-specific allograft tolerance by administration of recipient-derived immature dendritic cells and suboptimal immunosuppression. Transplantation 79: 969-972.
8. Bluestone, J. A., Thomson, A. W., Shevach, E. M., and Weiner, H. L. (2007) What does the future hold for cell-based tolerogenic therapy? Nat. Rev. Immunol. 7: 650-654.
9. Bonham, C. A., Peng, L., Liang, X., Chen, Z., Wang, L., Ma, L., Hackstein, H., Robbins, P. D., Thomson, A. W., Fung, J. J., Qian, S., and Lu, L. (2002) Marked prolongation of cardiac allograft survival by dendritic cells genetically engineered with NF-kappa B oligodeoxyribonucleotide decoys and adenoviral vectors encoding CTLA4-Ig. J. Immunol. 169: 3382-3391.
10. Bonifaz, L., Bonnyay, D., Mahnke, K., Rivera, M., Nussenzweig, M. C., and Steinman, R. M. (2002) Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompati-bility complex class I products and peripheral CD8+ T cell tolerance. J. Exp. Med. 196: 1627-1638.
11. Bonifaz, L. C., Bonnyay, D. P., Charalambous, A., Darguste, D. I., Fujii, S., Soares, H., Brimnes, M. K., Moltedo, B., Moran, T. M., and Steinman, R. M. (2004) in vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J. Exp. Med. 199: 815-824.
12. Boscardin, S. B., Hafalla, J. C., Masilamani, R. F., Kamphorst, A. O., Zebroski, H. A., Rai, U., Morrot, A., Zavala, F., Steinman, R. M., Nussenzweig, R. S., and Nussenzweig, M. C. (2006) Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses.J. Exp. Med. 203: 599-606.
13. Chaturvedi, V., Collison, L. W., Guy, C. S., Workman, C. J., and Vignali, D. A. (2011) Cutting edge: LC human regulatory T cells require IL-35 to mediate suppression and infectious tolerance. J. Immunol. 186: 6661-6666.
14. Chauveau, C., Remy, S., Royer, P. J., Hill, M., Tanguy-Royer, S., Hubert, F. X., Tesson, L., Brion, R., Beriou, G., Gregoire, M., Josien, R., Cuturi, M. C., and Anegon, I. (2005) Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression. Blood 106: 1694-1702.
15. Cheong, C., Choi, J. H., Vitale, L., He, L. Z., Trumpfheller, C., Bozzacco, L., Do, Y., Nchinda, G., Park, S. H., Dandamudi, D. B., Shrestha, E., Pack, M., Lee, H. W., Keler, T., Steinman, R. M., and Park, C. G. (2010a) Improved cellular and humoral immune responses in vivo following targeting of HIV Gag to dendritic cells within human anti-human DEC205 monoclonal antibody. Blood 116: 3828-3838.
16. Cheong, C., Matos, I., Choi, J. H., Dandamudi, D. B., Shrestha, E., Longhi, M. P., Jeffrey, K. L., Anthony, R. M., Kluger, C., Nchinda, G., Koh, H., Rodriguez, A., Idoyaga, J., Pack, M., Velinzon, K., Park, C. G., and Steinman, R. M. (2010b) Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209(+) dendritic cells for immune T cell areas. Cell 143: 416-429.
17. Chitta, S., Santambrogio, L., and Stern, L. J. (2008) GMCSF in the absence of other cytokines sustains human dendritic cell precursors with T cell regulatory activity and capacity to differentiate into functional dendritic cells. Immunol. Lett. 116: 41-54.
18. Collison, L. W., Chaturvedi, V., Henderson, A. L., Giacomin, P. R., Guy, C., Bankoti, J., Finkelstein, D., Forbes, K., Workman, C. J., Brown, S. A., Rehg, J. E., Jones, M. L., Ni, H. T., Artis, D., Turk, M. J., and Vignali, D. A. (2010) IL-35-mediated induction of a potent regulatory T cell population. Nat. Immunol. 11: 1093-1101.
19. Collison, L. W., Workman, C. J., Kuo, T. T., Boyd, K., Wang, Y., Vignali, K. M., Cross, R., Sehy, D., Blumberg, R. S., and Vignali, D. A. (2007) The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450: 566-569.
20. Correale, P., Campoccia, G., Tsang, K. Y., Micheli, L., Cusi, M. G., Sabatino, M., Bruni, G., Sestini, S., Petrioli, R., Pozzessere, D., Marsili, S., Fanetti, G., Giorgi, G., and Francini, G. (2001) Recruitment of dendritic cells and enhanced antigen-specific immune reactivity in cancer patients treated with hr-GM-CSF (Molgramostim) and hr-IL-2. results from a phase Ib clinical trial. Eur. J. Cancer 37: 892-902.
21. Dantal, J., Hourmant, M., Cantarovich, D., Giral, M., Blancho, G., Dreno, B., and Soulillou, J. P. (1998) Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence: randomised comparison of two cyclosporin regimens. Lancet 351: 623-628.
22. den Haan, J. M., Lehar, S. M., and Bevan, M. J. (2000) CD8(+) but not CD8(-) dendritic cells cross-prime cytotoxic T cells in vivo.J. Exp. Med. 192: 1685-1696.
23. Dhodapkar, M. V., and Steinman, R. M. (2002) Antigen-bearing immature dendritic cells induce peptide-specific CD8(+) regulatory T cells in vivo in humans. Blood 100: 174-177.
24. Dhodapkar, M. V., Steinman, R. M., Krasovsky, J., Munz, C., and Bhardwaj, N. (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J. Exp. Med. 193: 233-238.
25. Divito, S. J., Wang, Z., Shufesky, W. J., Liu, Q., Tkacheva, O. A., Montecalvo, A., Erdos, G., Larregina, A. T., and Morelli, A. E. (2010) Endogenous dendritic cells mediate the effects of intravenously injected therapeutic immunosuppressive dendritic cells in transplantation. Blood 116: 2694-2705.
26. Dudziak, D., Kamphorst, A. O., Heidkamp, G. F., Buchholz, V. R., Trumpfheller, C., Yamazaki, S., Cheong, C., Liu, K., Lee, H. W., Park, C. G., Steinman, R. M., and Nussenzweig, M. C. (2007) Differential antigen processing by dendritic cell subsets in vivo. Science 315: 107-111.
27. Emmer, P. M., van der Vlag, J., Adema, G. J., and Hilbrands, L. B. (2006) Dendritic cells activated by lipopolysaccharide after dex-amethasone treatment induce donor-specific allograft hypore-sponsiveness. Transplantation 81: 1451-1459.
28. Ezzelarab, M., and Thomson, A. W. (2011) Tolerogenic dendritic cells and their role in transplantation. Semin. Immunol. 23: 252-263.
29. Fujita, S., Sato, Y., Sato, K., Eizumi, K., Fukaya, T., Kubo, M., and Yamashita, N. (2007) Regulatory dendritic cells protect against cutaneous chronic graft-versus-host disease mediated through CD4+CD25+Foxp3+ regulatory T cells. Blood 110: 3793-3803.
30. Garrod, K. R., Chang, C. K., Liu, F. C., Brennan, T. V., Foster, R. D., and Kang, S. M. (2006) Targeted lym-phoid homing of dendritic cells is required for prolongation of allograft survival. J. Immunol. 177: 863-868.
31. Giannoukakis, N., Bonham, C. A., Qian, S., Chen, Z., Peng, L., Harnaha, J., Li, W., Thomson, A. W., Fung, J. J., Robbins, P. D., and Lu, L. (2000) Prolongation of cardiac allograft survival using dendritic cells treated with NF-κB decoy oligodeoxyribonucleotides. Mol. Ther. 1:430-437.
32. Giannoukakis, N., Phillips, B., Finegold, D., Harnaha, J., and Trucco, M. (2011) Phase, I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. Diabetes Care 34: 2026-2032.
33. Gregori, S., Tomasoni, D., Pacciani, V., Scirpoli, M., Battaglia, M., Magnani, C. F., Hauben, E., and Roncarolo, M. G. (2010) Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway. Blood 116: 935-944.
34. Griffin, M. D., Lutz, W., Phan, V. A., Bachman, L. A., McKean, D. J., and Kumar, R. (2001) Dendritic cell modulation by 1alpha, 25 dihydroxyvitamin D3 and its analogs: a vitamin D receptor-dependent pathway that promotes a persistent state of immaturity in vitro and in vivo. Proc. Natl. Acad. Sci. U.S.A. 98: 6800-6805.
35. Harry, R. A., Anderson, A. E., Isaacs, J. D., and Hilkens, C. M. (2010) Generation and characterisation of therapeutic tolerogenic dendritic cells for rheumatoid arthritis. Ann. Rheum. Dis. 69: 2042-2050.
36. Hawiger, D., Inaba, K., Dorsett, Y., Guo, M., Mahnke, K., Rivera, M., Ravetch, J. V., Steinman, R. M., and Nussenzweig, M. C. (2001) Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194: 769-779.
37. Herrera, O. B., Golshayan, D., Tibbott, R., Salcido Ochoa, F., James, M. J., Marelli-Berg, E M., and Lechler, R. I. (2004) A novel pathway of alloanti-gen presentation by dendritic cells. J. Immunol. 173: 4828-4837.
38. Hilkens, C. M., Isaacs, J. D., and Thomson, A. W. (2010) Development of dendritic cell-based immunotherapy for autoimmunity. Int. Rev. Immunol. 29: 156-183.
39. Hill, M., Tanguy-Royer, S., Royer, P., Chauveau, C., Asghar, K., Tesson, L., Lavainne, F., Remy, S., Brion, R., Hubert, E X., Heslan, M., Rimbert, M., Berthelot, L., Moffett, J. R., Josien, R., Gregoire, M., and Anegon, I. (2007) IDO expands human CD4+CD25high regulatory T cells by promoting maturation of LPS-treated dendritic cells. Eur. J. Immunol. 37: 3054-3062.
40. Hill, M., Thebault, P., Segovia, M., Louvet, C., Beriou, G., Tilly, G., Merieau, E., Anegon, I., Chiffoleau, E., and Cuturi, M. C. (2011) Cell therapy with autologous tolerogenic dendritic cells induces allograft tolerance through interferon-gamma and epstein-barr virus-induced gene 3. Am. J. Transplant 11: 2036-2045.
41. Hochrein, H., Shortman, K., Vremec, D., Scott, B., Hertzog, P., and O'Keeffe, M. (2001) Differential production of IL-12, IFN-alpha, and IFN-gamma by mouse dendritic cell subsets. J. Immunol. 166: 5448-5455.
42. Ilarregui, J. M., Croci, D. O., Bianco, G. A., Toscano, M. A., Salatino, M., Vermeulen, M. E., Geffner, J. R., and Rabinovich, G. A. (2009) Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregula-tory circuit involving interleukin 27 and interleukin 10. Nat. Immunol. 10: 981-991.
43. Kendal, A. R., Chen, Y., Regateiro, E S., Ma, J., Adams, E., Cobbold, S. P., Hori, S., and Waldmann, H. (2011) Sustained suppression by Foxp3+ regulatory T cells is vital for infectious transplantation tolerance. J. Exp. Med. 208: 2043-2053.
44. Kenna, T. J., Thomas, R., and Steptoe, R. J. (2008) Steady-state dendritic cells expressing cognate antigen terminate memory CD8+ T-cell responses. Blood 111:2091-2100.
45. Lechler, R., Chai, J. G., Marelli-Berg, E, and Lombardi, G. (2001) The contributions of T-cell anergy to peripheral T-cell tolerance. Immunology 103: 262-269.
46. Lee, Y R., Yang, I. H., Lee, Y H., Im, S. A., Song, S., Li, H., Han, K., Kim, K., Eo, S. K., and Lee, C. K. (2005) Cyclosporin A and tacrolimus, but not rapamycin, inhibit MHC-restricted antigen presentation pathways in dendritic cells. Blood 105: 3951-3955.
47. Li, M., Zhang, X., Zheng, X., Lian, D., Zhang, Z. X., Ge, W., Yang, J., Vladau, C., Suzuki, M., Chen, D., Zhong, R., Garcia, B., Jevnikar, A. M., and Min, W P. (2007) Immune modulation and tolerance induction by RelB-silenced dendritic cells through RNA interference. J. Immunol. 178: 5480-5487.
48. Lu, L., Qian, S., Hershberger, P. A., Rudert, W A., Lynch, D. H., and Thomson, A. W. (1997) Fas lig-and (CD95L) and B7 expression on dendritic cells provide counter-regulatory signals for T cell survival and proliferation. J. Immunol. 158: 5676-5684.
49. Lutz, M. B., Suri, R. M., Niimi, M., Ogilvie, A. L., Kukutsch, N. A., Rossner, S., Schuler, G., and Austyn, J. M. (2000) Immature dendritic cells generated with low doses of GM-CSF in the absence of IL-4 are maturation resistant and prolong allograft survival in vivo. Eur. J. Immunol. 30: 1813-1822.
50. Machen, J., Harnaha, J., Lakomy, R., Styche, A., Trucco, M., and Giannoukakis, N. (2004) Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells. J. Immunol. 173: 4331-4341.
51. Marti, H. P., Henschkowski, J., Laux, G., Vogt, B., Seiler, C., Opelz, G., and Frey, F. J. (2006) Effect of donor-specific transfusions on the outcome of renal allografts in the cyclo-sporine era. Transpl. Int. 19: 19-26.
52. Martin, E., Capini, C., Duggan, E., Lutzky, V. P., Stumbles, P., Pettit, A. R., O'Sullivan, B., and Thomas, R. (2007) Antigen-specific suppression of established arthritis in mice by dendritic cells deficient in NF-kappaB. Arthritis Rheum. 56: 2255-2266.
53. Martin, E., O'Sullivan, B., Low, P., and Thomas, R. (2003) Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10. Immunity 18: 155-167.
54. Mellor, A. L., Baban, B., Chandler, P., Marshall, B., Jhaver, K., Hansen, A., Koni, P. A., Iwashima, M., and Munn, D. H. (2003) Cutting edge: induced indoleamine 2, 3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J. Immunol. 171: 1652-1655.
55. Min, W. P., Gorczynski, R., Huang, X. Y., Kushida, M., Kim, P., Obataki, M., Lei, J., Rakesh, M. S., and Cattral, M. S. (2000) Dendritic cells genetically engineered to express Fas ligand induce donor-specific hyporesponsiveness and prolong allograft survival. J. Immunol. 164: 161-167.
56. Moreau, A., Chiffoleau, E., Beriou, G., Deschamps, J. Y., Heslan, M., Ashton-Chess, J., Rolling, F., Josien, R., Moullier, P., Cuturi, M. C., and Alliot-Licht, B. (2008) Superiority of bone marrow-derived dendritic cells over monocyte-derived ones for the expansion of regulatory T cells in the macaque. Transplantation 85: 1351-1356.
57. Moreau, A., Hill, M., Thebault, P., Deschamps, J. Y., Chiffoleau, E., Chauveau, C., Moullier, P., Anegon, I., Alliot-Licht, B., and Cuturi, M. C. (2009) Tolerogenic dendritic cells actively inhibit T cells through heme oxygenase-1 in rodents and in nonhuman primates. FASEB J. 23: 3070-3077.
58. Morelli, A. E., and Thomson, A. W. (2007) Tolerogenic dendritic cells and the quest for transplant tolerance. Nat. Rev. Immunol. 7: 610-621.
59. Mortara, L., Ploquin, M. J., Faye, A., Scott-Algara, D., Vaslin, B., Butor, C., Hosmalin, A., Barre-Sinoussi, F., Diop, O. M., and Muller-Trutwin, M. C. (2006) Phenotype and function of myeloid dendritic cells derived from African green monkey blood monocytes. J. Immunol. Methods 308: 138-155.
60. Niedbala, W., Wei, X. Q., Cai, B., Hueber, A. J., Leung, B. P., Mcinnes, I. B., and Liew, E Y (2007) IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur. J. Immunol. 37: 3021-3029.
61. O'Doherty, U., Ignatius, R., Bhardwaj, N., and Pope, M. (1997) Generation of monocyte-derived dendritic cells from precursors in rhesus macaque blood. J. Immunol. Methods 207: 185-194.
62. Peche, H., Trinite, B., Martinet, B., and Cuturi, M. C. (2005) Prolongation of heart allograft survival by immature dendritic cells generated from recipient type bone marrow progenitors. Am. J. Transplant 5: 255-267.
63. Pinchuk, L. M., Grouard-Vogel, G., Magaletti, D. M., Doty, R. T., Andrews, R. G., and Clark, E. A. (1999) Isolation and characterization of macaque dendritic cells from CD34(+) bone marrow progenitors. Cell. Immunol. 196: 34-40.
64. Probst, H. C., Lagnel, J., Kollias, G., andvan den Broek, M. (2003) Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity 18: 713-720.
65. Raiotach-Regue, D., Grau-Lopez, L., Naranjo-Gomez, M., Ramo-Tello, C., Pujol-Borrell, R., Martinez-Caceres, E., and Borras, E E. (2012) Stable antigen-specific T-cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients. Eur. J. Immunol. 42: 771-782.
66. Redman, B. G., Chang, A. E., Whitfield, J., Esper, P., Jiang, G., Braun, T., Roessler, B., and Mule, J. J. (2008) Phase Ib trial assessing autologous, tumor-pulsed dendritic cells as a vaccine administered with or without IL-2 in patients with metastatic melanoma. J. Immunother. 31: 591-598.
67. Reis e Sousa, C., Hieny, S., Scharton-Kersten, T., Jankovic, D., Charest, H., Germain, R. N., and Sher, A. (1997) In vivo microbial stimulation induces rapid CD40 ligand-independent production of inter-leukin 12 by dendritic cells and their redistribution to T cell areas. J. Exp. Med. 186: 1819-1829.
68. Schwartz, R. H. (1997) T cell clonal anergy. Curr. Opin. Immunol. 9: 351-357.
69. Segovia, M., Cuturi, M. C., and Hill, M. (2011) Preparation of mouse bone marrow-derived dendritic cells with immunoregulatory properties. MethodsMol. Biol. 677: 161-168.
70. Sharma, R. K., Rai, P. K., Kumar, A., Kumar, P., Gupta, A., Kher, V., Agrawal, S., and Bhandari, M. (1997) Role of preoperative donor-specific transfusion and cyclosporine in haplo-identical living related renal transplant recipients. Nephron 75: 20-24.
71. Shortman, K., Lahoud, M. H., and Caminschi, I. (2009) Improving vaccines by targeting antigens to dendritic cells. Exp. Mol. Med. 41: 61-66.
72. Shortman, K., and Naik, S. H. (2007) Steady-state and inflammatory dendritic-cell development. Nat. Rev. Immunol. 7: 19-30.
73. Smyth, L. A., Herrera, O. B., Golshayan, D., Lombardi, G., and Lechler, R. I. (2006) A novel pathway of antigen presentation by dendritic and endothelial cells: implications for allorecognition and infectious diseases. Transplantation 82: S15-S18.
74. Sordi, V., Bianchi, G., Buracchi, C., Mercalli, A., Marchesi, F., D'Amico, G., Yang, C. H., Luini, W., Vecchi, A., Mantovani, A., Allavena, P., and Piemonti, L. (2006) Differential effects of immunosuppressive drugs on chemokine receptor CCR7 in human monocyte-derived dendritic cells: selective upregulation by rapamycin. Transplantation 82: 826-834.
75. Tanriver, Y., Ratnasothy, K., Bucy, R. P., Lombardi, G., and Lechler, R. (2010) Targeting MHC class I monomers to dendritic cells inhibits the indirect pathway of allorecognition and the production of IgG alloantibodies leading to long-term allograft survival. J. Immunol. 184: 1757-1764.
76. Trumpfheller, C., Caskey, M., Nchinda, G., Longhi, M. P., Mizenina, O., Huang, Y., Schlesinger, S. J., Colonna, M., and Steinman, R. M. (2008) The microbial mimic poly IC induces durable and protective CD4+ T cell immunity together with a dendritic cell targeted vaccine. Proc. Natl. Acad. Sci. U.S.A. 105: 2574-2579.
77. Turnquist, H. R., Cardinal, J., Macedo, C., Rosborough, B. R., Sumpter, T. L., Geller, D. A., Metes, D., and Thomson, A. W. (2010) mTOR and GSK-3 shape the CD4+ T-cell stimulatory and differentiation capacity of myeloid DCs after exposure to LPS. Blood 115: 4758-4769.
78. Turnquist, H. R., Raimondi, G., Zahorchak, A. F., Fischer, R. T., Wang, Z., and Thomson, A. W. (2007) Rapamycin-conditioned dendritic cells are poor stimulators of allogeneic CD4+ T cells, but enrich for antigen-specific Foxp3+ T regulatory cells and promote organ transplant tolerance. J. Immunol. 178: 7018-7031.
79. Wakkach, A., Fournier, N., Brun, V., Breittmayer, J. P., Cottrez, F., and Groux, H. (2003) Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18: 605-617.
80. Wang, Z., Divito, S. J., Shufesky, W. J., Sumpter, T., Wang, H., Tkacheva, O. A., Wang, W., Liu, C., Larregina, A. T., and Morelli, A. E. (2012) Dendritic cell therapies in transplantation revisited: deletion of recipient DCs deters the effect of therapeutic DCs. Am. I Transplant, doi: 10.1111/j.1600-6143.2012.04060.x. [Epub ahead of print].
81. Yamano, T., Watanabe, S., Hasegawa, H., Suzuki, T., Abe, R., Tahara, H., Nitta, T., Ishimaru, N., Sprent, J., and Kishimoto, H. (2011) Ex vivo-expanded DCs induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin grafts. Blood 117: 2640-2648.
82. Yamazaki, S., Iyoda, T., Tarbell, K., Olson, K., Velinzon, K., Inaba, K., and Steinman, R. M. (2003) Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells. J. Exp. Med. 198: 235-247.
83. Yang, J., Bernier, S. M., Ichim, T. E., Li, M., Xia, X., Zhou, D., Huang, X., Strejan, G. H., White, D. J., Zhong, R., and Min, W. P. (2003) LF15-0195 generates tolerogenic dendritic cells by suppression of NF-kappaB signaling through inhibition of IKK activity. J. Leukoc. Biol. 74: 438-447.
84. Yu, G., Xu, X., Vu, M. D., Kilpatrick, E. D., and Li, X. C. (2006) NK cells promote transplant tolerance by killing donor antigen-presenting cells. J. Exp. Med. 203: 1851-1858.
85. Zahorchak, A. F., Kean, L. S., Tokita, D., Turnquist, H. R., Abe, M., Finke, J., Hamby, K., Rigby, M. R., Larsen, C. P., and Thomson, A. W. (2007) Infusion of stably immature monocyte-derived dendritic cells plus CTLA4Ig modulates alloim-mune reactivity in rhesus macaques. Transplantation 84: 196-206.