Dendritic cell-based therapy in Type 1 diabetes mellitus

Expert Review of Clinical Immunology

Volumn 5, Issue 3, 2009, Pages 325-339

  Phillips, Brett ^a   Giannoukakis, Nick ^a   Trucco, Massimo ^a  

^a CHILDREN S HOSPITAL OF PITTSBURGH   (United States)

Author keywords

Autoimmunity; Dendritic cell; Immunosuppression; Immunotherapy; Type 1 diabetes

Indexed keywords

AUTOIMMUNITY; DENDRITIC CELL; GRAFT SURVIVAL; HUMAN; IMMUNOTHERAPY; INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; REVIEW;

EID: 70349674750     PISSN: 1744666X     EISSN: None     Source Type: Journal    
DOI: 10.1586/eci.09.8     Document Type: Review

References (270)

1. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 392, 245-252 (1998).
2. Lutz MB, Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol. 23, 445-449 (2002).
3. Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Ann. Rev. Immunol. 21, 685-711 (2003).
4. Steinman RM, Turley S, Mellman I, Inaba K. The induction of tolerance by dendritic cells that have captured apoptotic cells. J. Exp. Med. 191, 411-416 (2000).
5. Vlad G, Cortesini R, Suciu-Foca N. License to heal: bidirectional interaction of antigen-specific regulatory T cells and tolerogenic APC. J. Immunol. 174, 5907-5914 (2005).
6. Apostolou I, Verginis P, Kretschmer K, Polansky J, Huhn J, von Boehmer H. Peripherally induced Treg: mode, stability, and role in specific tolerance. J. Clin. Immunol. 28, 619-624 (2008).
7. Chappert P, Leboeuf M, Rameau P et al. Antigen-driven interactions with dendritic cells and expansion of Foxp3+ regulatory T cells occur in the absence of inflammatory signals. J. Immunol. 180, 327-334 (2008).
8. Lonial S, Torre C, David E, Harris W, Arellano M, Waller EK. Regulation of alloimmune responses by dendritic cell subsets. Exp. Hematol. 36, 1309-1317 (2008).
9. Marguti I, Yamamoto GL, da Costa TB, Rizzo LV, de Moraes LV. Expansion of CD4+ CD25+ Foxp3+ T cells by bone marrow-derived dendritic cells. Immunology 127(1), 50-61 (2009).
10. Morelli AE, Thomson AW. Tolerogenic dendritic cells and the quest for transplant tolerance. Nat. Rev. Immunol. 7, 610-621 (2007).
11. Velasquez-Lopera MM, Correa LA, Garcia LF. Human spleen contains different subsets of dendritic cells and regulatory T lymphocytes. Clin. Exp. Immunol. 154, 107-114 (2008).
12. Smits HH, de Jong EC, Wierenga EA, Kapsenberg ML. Different faces of regulatory DCs in homeostasis and immunity. Trends Immunol. 26, 123-129 (2005).
13. Smits HH, Engering A, van der Kleij D et al. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J. Allergy Clin. Immunol. 115, 1260-1267 (2005).
14. Yamazaki S, Iyoda T, Tarbell K et al. Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells. J. Exp. Med. 198, 235-247 (2003).
15. Inaba K, Metlay JP, Crowley MT, Steinman RM. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J. Exp. Med. 172, 631-640 (1990).
16. Kubach J, Becker C, Schmitt E et al. Dendritic cells: sentinels of immunity and tolerance. Int. J. Hematol. 81, 197-203 (2005).
17. Steinman RM. Some interfaces of dendritic cell biology. APMIS 111, 675-697 (2003).
18. Steinman RM, Bonifaz L, Fujii S et al. The innate functions of dendritic cells in peripheral lymphoid tissues. Adv. Exp. Med. Biol. 560, 83-97 (2005).
19. Steinman RM, Nussenzweig MC. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl Acad. Sci. USA 99, 351-358 (2002).
20. Liu YJ. Dendritic cell subsets and lineages, and their functions in innate and adaptive immunity. Cell 106, 259-262 (2001).
21. Liu YJ, Kanzler H, Soumelis V, Gilliet M. Dendritic cell lineage, plasticity and cross-regulation. Nat. Immunol. 2, 585-589 (2001).
22. Bluestone JA. Costimulation and its role in organ transplantation. Clin. Transplant. 10, 104-109 (1996).
23. Clarkson MR, Sayegh MH. T-cell costimulatory pathways in allograft rejection and tolerance. Transplantation 80, 555-563 (2005).
24. Kishimoto K, Dong VM, Sayegh MH. The role of costimulatory molecules as targets for new immunosuppressives in transplantation. Curr. Opin. Urol. 10, 57-62 (2000).
25. Lenschow DJ, Walunas TL, Bluestone JA. CD28/B7 system of T cell costimulation. Ann. Rev. Immunol. 14, 233-258 (1996).
26. Rothstein DM, Sayegh MH. T-cell costimulatory pathways in allograft rejection and tolerance. Immunol. Rev. 196, 85-108 (2003).
27. Sayegh MH, Turka LA. T cell costimulatory pathways: promising novel targets for immunosuppression and tolerance induction. J. Am. Soc. Nephrol. 6, 1143-1150 (1995).
28. Manz MG, Traver D, Akashi K et al. Dendritic cell development from common myeloid progenitors. Ann. NY Acad. Sci. 938, 167-173; discussion 173-174 (2001).
29. Manz MG, Traver D, Miyamoto T, Weissman IL, Akashi K. Dendritic cell potentials of early lymphoid and myeloid progenitors. Blood 97, 3333-3341 (2001).
30. Manfredi AA, Sabbadini MG, Rovere-Querini P. Dendritic cells and the shadow line between autoimmunity and disease. Arthritis Rheum. 52, 11-15 (2005).
31. Suciu-Foca N, Manavalan JS, Scotto L et al. Molecular characterization of allospecific T suppressor and tolerogenic dendritic cells: review. Int. Immunopharmacol. 5, 7-11 (2005).
32. Komulainen J, Knip M, Lounamaa R et al. Poor b-cell function after the clinical manifestation of Type 1 diabetes in children initially positive for islet cell specific autoantibodies. The Childhood Diabetes in Finland Study Group. Diabet. Med. 14, 532-537 (1997).
33. Lampeter EF, Klinghammer A, Scherbaum WA et al. The Deutsche Nicotinamide Intervention Study: an attempt to prevent Type 1 diabetes. DENIS Group. Diabetes 47, 980-984 (1998).
34. Larsen MO, Rolin B, Gotfredsen CF, Carr RD, Holst JJ. Reduction of b cell mass: partial insulin secretory compensation from the residual b cell population in the nicotinamide-streptozotocin Gottingen minipig after oral glucose in vivo and in the perfused pancreas. Diabetologia 47, 1873-1878 (2004).
35. Lohmann T, Kellner K, Verlohren HJ et al. Titre and combination of ICA and autoantibodies to glutamic acid decarboxylase discriminate two clinically distinct types of latent autoimmune diabetes in adults (LADA). Diabetologia 44, 1005-1010 (2001).
36. Mayer A, Rharbaoui F, Thivolet C, Orgiazzi J, Madec AM. The relationship between peripheral T cell reactivity to insulin, clinical remissions and cytokine production in Type 1 (insulin-dependent) diabetes mellitus. J. Clin. Endocrinol. Metab. 84, 2419-2424 (1999).
37. Papoz L, Lenegre F, Hors J et al. Probability of remission in individual in early adult insulin dependent diabetic patients. Results from the Cyclosporine Diabetes French Study Group. Diabetes Metab. 16, 303-310 (1990).
38. Petrone A, Galgani A, Spoletini M et al. Residual insulin secretion at diagnosis of Type 1 diabetes is independently associated with both, age of onset and HLA genotype. Diabetes Metab. Res. Rev. 21, 271-275 (2005).
39. Rasmussen SB, Sorensen TS, Hansen JB, Mandrup-Poulsen T, Hornum L, Markholst H. Functional rest through intensive treatment with insulin and potassium channel openers preserves residual b-cell function and mass in acutely diabetic BB rats. Horm. Metab. Res. 32, 294-300 (2000).
40. Shimada A, Imazu Y, Morinaga S et al. T-cell insulitis found in anti-GAD65+ diabetes with residual b-cell function. A case report. Diabetes Care 22, 615-617 (1999).
41. Sreenan S, Pick AJ, Levisetti M, Baldwin AC, Pugh W, Polonsky KS. Increased b-cell proliferation and reduced mass before diabetes onset in the nonobese diabetic mouse. Diabetes 48, 989-996 (1999).
42. Weets I, Truyen I, Verschraegen I et al. Sex-and season-dependent differences in C-peptide levels at diagnosis of immunemediated Type 1 diabetes. Diabetologia 49, 1158-1162 (2006).
43. Arnush M, Scarim AL, Heitmeier MR, Kelly CB, Corbett JA. Potential role of resident islet macrophage activation in the initiation of autoimmune diabetes. J. Immunol. 160, 2684-2691 (1998).
44. Corbett JA, McDaniel ML. Reversibility of interleukin-1 b-induced islet destruction and dysfunction by the inhibition of nitric oxide synthase. Biochem. J. 299(Pt 3), 719-724 (1994).
45. Corbett JA, Wang JL, Hughes JH et al. Nitric oxide and cyclic GMP formation induced by interleukin 1 b in islets of Langerhans. Evidence for an effector role of nitric oxide in islet dysfunction. Biochem. J. 287(Pt 1), 229-235 (1992).
46. Corbett JA, Wang JL, Misko TP, Zhao W, Hickey WF, McDaniel ML. Nitric oxide mediates IL-1 b-induced islet dysfunction and destruction: prevention by dexamethasone. Autoimmunity 15, 145-153 (1993).
47. Sai P, Rivereau AS, Granier C, Haertle T, Martignat L. Immunization of non-obese diabetic (NOD) mice with glutamic acid decarboxylase-derived peptide 524-543 reduces cyclophosphamide-accelerated diabetes. Clin. Exp. Immunol. 105, 330-337 (1996).
48. McDaniel ML, Kwon G, Hill JR, Marshall CA, Corbett JA. Cytokines and nitric oxide in islet inflammation and diabetes. Proc. Soc. Exp. Biol. Med. 211, 24-32 (1996).
49. Scarim AL, Heitmeier MR, Corbett JA. Irreversible inhibition of metabolic function and islet destruction after a 36-hour exposure to interleukin-1b. Endocrinology 138, 5301-5307 (1997).
50. Trudeau JD, Dutz JP, Arany E, Hill DJ, Fieldus WE, Finegood DT. Neonatal b-cell apoptosis: a trigger for autoimmune diabetes? Diabetes 49, 1-7 (2000).
51. Oldstone MB. Molecular mimicry and autoimmune disease. Cell 50, 819-820 (1987).
52. Oldstone MB. Virus-induced autoimmunity: molecular mimicry as a route to autoimmune disease. J. Autoimmun. 2 (Suppl.), 187-194 (1989).
53. Oldstone MB. Molecular mimicry as a mechanism for the cause and a probe uncovering etiologic agent(s) of autoimmune disease. Curr. Top. Microbiol. Immunol. 145, 127-135 (1989).
54. Conrad B, Weidmann E, Trucco G et al. Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology. Nature 371, 351-355 (1994).
55. Conrad B, Trucco M. Superantigens as etiopathogenetic factors in the development of insulin-dependent diabetes mellitus. Diabetes Metab. Rev. 10, 309-338 (1994).
56. Jansen A, Homo-Delarche F, Hooijkaas H, Leenen PJ, Dardenne M, Drexhage HA. Immunohistochemical characterization of monocytes-macrophages and dendritic cells involved in the initiation of the insulitis and b-cell destruction in NOD mice. Diabetes 43, 667-675 (1994).
57. Jansen A, Rosmalen JG, Homo-Delarche F, Dardenne M, Drexhage HA. Effect of prophylactic insulin treatment on the number of ER-MP23+ macrophages in the pancreas of NOD mice. Is the prevention of diabetes based on b-cell rest? J. Autoimmun. 9, 341-348 (1996).
58. Lo D, Reilly CR, Scott B, Liblau R, McDevitt HO, Burkly LC. Antigenpresenting cells in adoptively transferred and spontaneous autoimmune diabetes. Eur. J. Immunol. 23, 1693-1698 (1993).
59. Clare-Salzler M, Mullen Y. Marked dendritic cell-T cell cluster formation in the pancreatic lymph node of the non-obese diabetic mouse. Immunology 76, 478-484 (1992).
60. Hoglund P, Mintern J, Waltzinger C, Heath W, Benoist C, Mathis D. Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes. J. Exp. Med. 189, 331-339 (1999).
61. Shimizu J, Carrasco-Marin E, Kanagawa O, Unanue ER. Relationship between b cell injury and antigen presentation in NOD mice. J. Immunol. 155, 4095-4099 (1995).
62. Green EA, Eynon EE, Flavell RA. Local expression of TNF-a in neonatal NOD mice promotes diabetes by enhancing presentation of islet antigens. Immunity 9, 733-743 (1998).
63. Dahlen E, Dawe K, Ohlsson L, Hedlund G. Dendritic cells and macrophages are the first and major producers of TNF-a in pancreatic islets in the nonobese diabetic mouse. J. Immunol. 160, 3585-3593 (1998).
64. Ehl S, Hombach J, Aichele P et al. Viral and bacterial infections interfere with peripheral tolerance induction and activate CD8+ T cells to cause immunopathology. J. Exp. Med. 187, 763-774 (1998).
65. Ludewig B, Ehl S, Karrer U, Odermatt B, Hengartner H, Zinkernagel RM. Dendritic cells efficiently induce protective antiviral immunity. J. Virol. 72, 3812-3818 (1998).
66. Ludewig B, Odermatt B, Landmann S, Hengartner H, Zinkernagel RM. Dendritic cells induce autoimmune diabetes and maintain disease via de novo formation of local lymphoid tissue. J. Exp. Med. 188, 1493-1501 (1998).
67. Christen U, von Herrath MG. Transgenic animal models for Type 1 diabetes: linking a tetracycline-inducible promoter with a virus-inducible mouse model. Transgenic. Res. 11, 587-595 (2002).
68. Christen U, von Herrath MG. Manipulating the Type 1 vs Type 2 balance in Type 1 diabetes. Immunol. Res. 30, 309-325 (2004).
69. Christen U, von Herrath MG. Induction, acceleration or prevention of autoimmunity by molecular mimicry. Mol. Immunol. 40, 1113-1120 (2004).
70. von Herrath MG. Regulation of virally induced autoimmunity and immunopathology: contribution of LCMV transgenic models to understanding autoimmune insulin-dependent diabetes mellitus. Curr. Top. Microbiol. Immunol. 263, 145-175 (2002).
71. Gallucci S, Matzinger P. Danger signals: SOS to the immune system. Curr. Opin. Immunol. 13, 114-119 (2001).
72. Matzinger P. Tolerance, danger, and the extended family. Ann. Rev. Immunol. 12, 991-1045 (1994).
73. Matzinger P. An innate sense of danger. Semin. Immunol. 10, 399-415 (1998).
74. Matzinger P. Essay 1: the Danger Model in its historical context. Scand J. Immunol. 54, 4-9 (2001).
75. Matzinger P. An innate sense of danger. Ann. NY Acad. Sci. 961, 341-342 (2002).
76. Marleau AM, Singh B. Myeloid dendritic cells in non-obese diabetic mice have elevated costimulatory and T helper-1-inducing abilities. J. Autoimmun. 19, 23-35 (2002).
77. Sen P, Bhattacharyya S, Wallet M et al. NF-kB hyperactivation has differential effects on the APC function of nonobese diabetic mouse macrophages. J. Immunol. 170, 1770-1780 (2003).
78. Weaver DJ Jr, Poligone B, Bui T, Abdel-Motal UM, Baldwin AS Jr, Tisch R. Dendritic cells from nonobese diabetic mice exhibit a defect in NF-kB regulation due to a hyperactive IkB kinase. J. Immunol. 167, 1461-1468 (2001).
79. Wheat W, Kupfer R, Gutches DG et al. Increased NF-kB activity in B cells and bone marrow-derived dendritic cells from NOD mice. Eur. J. Immunol. 34, 1395-1404 (2004).
80. Boudaly S, Morin J, Berthier R, Marche P, Boitard C. Altered dendritic cells (DC) might be responsible for regulatory T cell imbalance and autoimmunity in nonobese diabetic (NOD) mice. Eur. Cytokine Netw. 13, 29-37 (2002).
81. Nikolic T, Bunk M, Drexhage HA, Leenen PJ. Bone marrow precursors of nonobese diabetic mice develop into defective macrophage-like dendritic cells in vitro. J. Immunol. 173, 4342-4351 (2004).
82. Strid J, Lopes L, Marcinkiewicz J et al. A defect in bone marrow derived dendritic cell maturation in the nonobese diabetic mouse. Clin. Exp. Immunol. 123, 375-381 (2001).
83. Eibl N, Spatz M, Fischer GF et al. Impaired primary immune response in Type-1 diabetes: results from a controlled vaccination study. Clin. Immunol. 103, 249-259 (2002).
84. McMahon MM, Bistrian BR. Host defenses and susceptibility to infection in patients with diabetes mellitus. Infect. Dis. Clin. North Am. 9, 1-9 (1995).
85. Wheat LJ. Infection and diabetes mellitus. Diabetes Care 3, 187-197 (1980).
86. Peng R, Li Y, Brezner K, Litherland S, Clare-Salzler MJ. Abnormal peripheral blood dendritic cell populations in Type 1 diabetes. Ann. NY Acad. Sci. 1005, 222-225 (2003).
87. Summers KL, Behme MT, Mahon JL, Singh B. Characterization of dendritic cells in humans with Type 1 diabetes. Ann. NY Acad. Sci. 1005, 226-229 (2003).
88. Summers KL, Marleau AM, Mahon JL, McManus R, Hramiak I, Singh B. Reduced IFN-a secretion by blood dendritic cells in human diabetes. Clin. Immunol. 121, 81-89 (2006).
89. Coates PT, Thomson AW. Dendritic cells, tolerance induction and transplant outcome. Am. J. Transplant. 2, 299-307 (2002).
90. Davis ID, Jefford M, Parente P, Cebon J. Rational approaches to human cancer immunotherapy. J. Leukoc. Biol. 73, 3-29 (2003).
91. Di Nicola M, Anichini A, Mortarini R, Bregni M, Parmiani G, Gianni AM. Human dendritic cells: natural adjuvants in antitumor immunotherapy. Cytokines Cell Mol. Ther. 4, 265-273 (1998).
92. Hackstein H, Morelli AE, Thomson AW. Designer dendritic cells for tolerance induction: guided not misguided missiles. Trends Immunol. 22, 437-442 (2001).
93. Hardin JA. Dendritic cells: potential triggers of autoimmunity and targets for therapy. Ann. Rheum. Dis. 64(Suppl 4), iv86-iv90 (2005).
94. Morelli AE, Thomson AW. Dendritic cells: regulators of alloimmunity and opportunities for tolerance induction. Immunol. Rev. 196, 125-146 (2003).
95. Nouri-Shirazi M, Thomson AW. Dendritic cells as promoters of transplant tolerance. Expert Opin. Biol. Ther. 6, 325-339 (2006).
96. Paul S, Calmels B, Acres RB. Improvement of adoptive cellular immunotherapy of human cancer using ex vivo gene transfer. Curr. Gene Ther. 2, 91-100 (2002).
97. Steinman RM, Inaba K, Turley S, Pierre P, Mellman I. Antigen capture, processing, and presentation by dendritic cells: recent cell biological studies. Hum. Immunol. 60, 562-567 (1999).
98. Feili-Hariri M, Dong X, Alber SM, Watkins SC, Salter RD, Morel PA. Immunotherapy of NOD mice with bone marrow-derived dendritic cells. Diabetes 48, 2300-2308 (1999).
99. Bottino R, Lemarchand P, Trucco M, Giannoukakis N. Gene-and cell-based therapeutics for Type I diabetes mellitus. Gene Ther. 10, 875-889 (2003).
100. Chen D, Sung R, Bromberg JS. Gene therapy in transplantation. Transpl. Immunol. 9, 301-314 (2002).
101. Giannoukakis N, Rudert WA, Robbins PD, Trucco M. Targeting autoimmune diabetes with gene therapy. Diabetes 48, 2107-2121 (1999).
102. Giannoukakis N, Thomson A, Robbins P. Gene therapy in transplantation. Gene Ther. 6, 1499-1511 (1999).
103. Giannoukakis N, Trucco M. Gene therapy for Type 1 diabetes. Am. J. Ther. 12, 512-528 (2005).
104. Tarner IH, Fathman CG. The potential for gene therapy in the treatment of autoimmune disease. Clin. Immunol. 104, 204-216 (2002).
105. Tarner IH, Slavin AJ, McBride J et al. Treatment of autoimmune disease by adoptive cellular gene therapy. Ann. NY Acad. Sci. 998, 512-519 (2003).
106. Trucco M, Robbins PD, Thomson AW, Giannoukakis N. Gene therapy strategies to prevent autoimmune disorders. Curr. Gene Ther. 2, 341-354 (2002).
107. Chen W. Dendritic cells and (CD4+) CD25+ T regulatory cells: crosstalk between two professionals in immunity versus tolerance. Front. Biosci. 11, 1360-1370 (2006).
108. Hugues S, Boissonnas A, Amigorena S, Fetler L. The dynamics of dendritic cell-T cell interactions in priming and tolerance. Curr. Opin. Immunol. 18, 491-495 (2006).
109. Beissert S, Schwarz A, Schwarz T. Regulatory T cells. J. Invest. Dermatol. 126, 15-24 (2006).
110. Enk AH. DCs and cytokines cooperate for the induction of Tregs. Ernst Schering Res. Found. Workshop 56, 97-106 (2006).
111. Huber S, Schramm C. TGF-b and CD4+CD25+ regulatory T cells. Front. Biosci. 11, 1014-1023 (2006).
112. Lohr J, Knoechel B, Abbas AK. Regulatory T cells in the periphery. Immunol. Rev. 212, 149-162 (2006).
113. Roncarolo MG, Gregori S, Battaglia M, Bacchetta R, Fleischhauer K, Levings MK. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol. Rev. 212, 28-50 (2006).
114. Shevach EM, DiPaolo RA, Andersson J, Zhao DM, Stephens GL, Thornton AM. The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells. Immunol. Rev. 212, 60-73 (2006).
115. Tang Q, Bluestone JA. Regulatory T-cell physiology and application to treat autoimmunity. Immunol. Rev. 212, 217-237 (2006).
116. Verhagen J, Blaser K, Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy: T-regulatory cells and more. Immunol. Allergy Clin. North Am. 26, 207-231, vi (2006).
117. Zhang L, Yi H, Xia XP, Zhao Y. Transforming growth factor-b: an important role in CD4+CD25+ regulatory T cells and immune tolerance. Autoimmunity 39, 269-276 (2006).
118. Anderson CC, Chan WF. Mechanisms and models of peripheral CD4 T cell selftolerance. Front. Biosci. 9, 2947-2963 (2004).
119. Balomenos D, Martinez AC. Cell-cycle regulation in immunity, tolerance and autoimmunity. Immunol. Today 21, 551-555 (2000).
120. Brennan PJ, Saouaf SJ, Greene MI, Shen Y. Anergy and suppression as coexistent mechanisms for the maintenance of peripheral T cell tolerance. Immunol. Res. 27, 295-302 (2003).
121. Goodnow CC, Sprent J, Fazekas de St Groth B, Vinuesa CG. Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature 435, 590-597 (2005).
122. Lechler R, Chai JG, Marelli-Berg F, Lombardi G. The contributions of T-cell anergy to peripheral T-cell tolerance. Immunology 103, 262-269 (2001).
123. Lechler R, Chai JG, Marelli-Berg F, Lombardi G. T-cell anergy and peripheral T-cell tolerance. Philos. Trans. R. Soc. Lond. B Biol. Sci. 356, 625-637 (2001).
124. Saouaf SJ, Brennan PJ, Shen Y, Greene MI. Mechanisms of peripheral immune tolerance: conversion of the immune to the unresponsive phenotype. Immunol. Res. 28, 193-199 (2003).
125. Singh NJ, Schwartz RH. Primer: mechanisms of immunologic tolerance. Nat. Clin. Pract. Rheumatol. 2, 44-52 (2006).
126. Battaglia M, Gregori S, Bacchetta R, Roncarolo MG. Tr1 cells: from discovery to their clinical application. Semin. Immunol. 18, 120-127 (2006).
127. Mennechet FJ, Uze G. Interferon-l-treated dendritic cells specifically induce proliferation of FOXP3-expressing suppressor T cells. Blood 107, 4417-4423 (2006).
128. Rutella S, Bonanno G, Procoli A et al. Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features. Blood 108, 218-227 (2006).
129. Vigouroux S, Yvon E, Biagi E, Brenner MK. Antigen-induced regulatory T cells. Blood 104, 26-33 (2004).
130. Watanabe N, Wang YH, Lee HK et al. Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 436, 1181-1185 (2005).
131. Yvon ES, Vigouroux S, Rousseau RF et al. Overexpression of the Notch ligand, Jagged-1, induces alloantigen-specific human regulatory T cells. Blood 102, 3815-3821 (2003). (Pubitemid 37409406)
132. Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J. Exp. Med. 193, 233-238 (2001).
133. Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH. Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J. Exp. Med. 192, 1213-1222 (2000).
134. Brinster C, Shevach EM. Bone marrowderived dendritic cells reverse the anergic state of CD4+CD25+ T cells without reversing their suppressive function. J. Immunol. 175, 7332-7340 (2005).
135. Tarbell KV, Yamazaki S, Olson K, Toy P, Steinman RM. CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J. Exp. Med. 199, 1467-1477 (2004).
136. DiPaolo RJ, Brinster C, Davidson TS, Andersson J, Glass D, Shevach EM. Autoantigen-specific TGFb-induced Foxp3+ regulatory T cells prevent autoimmunity by inhibiting dendritic cells from activating autoreactive T cells. J. Immunol. 179, 4685-4693 (2007).
137. Lehner T. Special regulatory T cell review: the resurgence of the concept of contrasuppression in immunoregulation. Immunology 123, 40-44 (2008).
138. Onishi Y, Fehervari Z, Yamaguchi T, Sakaguchi S. Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc. Natl Acad. Sci. USA 105, 10113-10118 (2008).
139. Xia G, He J, Leventhal JR. Ex vivo-expanded natural CD4+CD25+ regulatory T cells synergize with host T-cell depletion to promote long-term survival of allografts. Am. J. Transplant 8, 298-306 (2008).
140. Harnaha J, Machen J, Wright M et al. Interleukin-7 is a survival factor for CD4+ CD25+ T-cells and is expressed by diabetes-suppressive dendritic cells. Diabetes 55, 158-170 (2006).
141. Ma L, Qian S, Liang X et al. Prevention of diabetes in NOD mice by administration of dendritic cells deficient in nuclear transcription factor-kB activity. Diabetes 52, 1976-1985 (2003).
142. Machen J, Harnaha J, Lakomy R, Styche A, Trucco M, Giannoukakis N. Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells. J. Immunol. 173, 4331-4341 (2004).
143. Phillips B, Nylander K, Harnaha J et al. A microsphere-based vaccine prevents and reverses new-onset autoimmune diabetes. Diabetes 57, 1544-1555 (2008).
144. Gordon EJ, Wicker LS, Peterson LB et al. Autoimmune diabetes and resistance to xenograft transplantation tolerance in NOD mice. Diabetes 54, 107-115 (2005).
145. Markees TG, Serreze DV, Phillips NE et al. NOD mice have a generalized defect in their response to transplantation tolerance induction. Diabetes 48, 967-974 (1999).
146. Pearson T, Markees TG, Serreze DV et al. Genetic disassociation of autoimmunity and resistance to costimulation blockadeinduced transplantation tolerance in nonobese diabetic mice. J. Immunol. 171, 185-195 (2003).
147. Pearson T, Markees TG, Serreze DV et al. Islet cell autoimmunity and transplantation tolerance: two distinct mechanisms? Ann. NY Acad. Sci. 1005, 148-156 (2003).
148. Pearson T, Markees TG, Wicker LS et al. NOD congenic mice genetically protected from autoimmune diabetes remain resistant to transplantation tolerance induction. Diabetes 52, 321-326 (2003).
149. Rossini AA. Autoimmune diabetes and the circle of tolerance. Diabetes 53, 267-275 (2004).
150. Rossini AA, Mordes JP, Greiner DL, Stoff JS. Islet cell transplantation tolerance. Transplantation 72, S43-S46 (2001).
151. Seung E, Mordes JP, Greiner DL, Rossini AA. Induction of tolerance for islet transplantation for Type 1 diabetes. Curr. Diab. Rep. 3, 329-335 (2003).
152. Banchereau J, Fay J, Pascual V, Palucka AK. Dendritic cells: controllers of the immune system and a new promise for immunotherapy. Novartis Found. Symp. 252, 226-235 (2003).
153. Blanco P, Palucka AK, Pascual V, Banchereau J. Dendritic cells and cytokines in human inflammatory and autoimmune diseases. Cytokine Growth Factor Rev. 19, 41-52 (2008).
154. Hsu W, Shu SA, Gershwin E, Lian ZX. The current immune function of hepatic dendritic cells. Cell Mol. Immunol. 4, 321-328 (2007).
155. Kuwana M. Induction of anergic and regulatory T cells by plasmacytoid dendritic cells and other dendritic cell subsets. Hum. Immunol. 63, 1156-1163 (2002).
156. Kuwana M, Kaburaki J, Wright TM, Kawakami Y, Ikeda Y. Induction of antigen-specific human CD4+ T cell anergy by peripheral blood DC2 precursors. Eur. J. Immunol. 31, 2547-2557 (2001).
157. Lian ZX, Okada T, He XS et al. Heterogeneity of dendritic cells in the mouse liver: identification and characterization of four distinct populations. J. Immunol. 170, 2323-2330 (2003).
158. Liang X, Ma L, Thai NL, Fung JJ, Qian S, Lu L. The role of liver-derived regulatory dendritic cells in prevention of Type 1 diabetes. Immunology 120, 251-260 (2007).
159. Monrad S, Kaplan MJ. Dendritic cells and the immunopathogenesis of systemic lupus erythematosus. Immunol. Res. 37, 135-145 (2007).
160. Vuckovic S, Withers G, Harris M et al. Decreased blood dendritic cell counts in Type 1 diabetic children. Clin. Immunol. 123, 281-288 (2007).
161. Wakkach A, Fournier N, Brun V, Breittmayer JP, Cottrez F, Groux H. Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18, 605-617 (2003).
162. Young JW, Merad M, Hart DN. Dendritic cells in transplantation and immune-based therapies. Biol. Blood Marrow Transplant. 13, 23-32 (2007).
163. Arpinati M, Chirumbolo G, Urbini B, Perrone G, Rondelli D, Anasetti C. Role of plasmacytoid dendritic cells in immunity and tolerance after allogeneic hematopoietic stem cell transplantation. Transpl. Immunol. 11, 345-356 (2003).
164. Gilliet M, Liu YJ. Human plasmacytoidderived dendritic cells and the induction of T-regulatory cells. Hum. Immunol. 63, 1149-1155 (2002). (Pubitemid 36025989)
165. Hochrein H, O'Keeffe M, Wagner H. Human and mouse plasmacytoid dendritic cells. Hum. Immunol. 63, 1103-1110 (2002).
166. Ito T, Liu YJ, Kadowaki N. Functional diversity and plasticity of human dendritic cell subsets. Int. J. Hematol. 81, 188-196 (2005).
167. Magyarics Z, Rajnavolgyi E. Professional type I interferon-producing cells: a unique subpopulation of dendritic cells. Acta Microbiol. Immunol. Hung. 52, 443-462 (2005).
168. Palucka AK, Banchereau J, Blanco P, Pascual V. The interplay of dendritic cell subsets in systemic lupus erythematosus. Immunol. Cell Biol. 80, 484-488 (2002).
169. Rossi M, Arpinati M, Rondelli D, Anasetti C. Plasmacytoid dendritic cells: do they have a role in immune responses after hematopoietic cell transplantation? Hum. Immunol. 63, 1194-1200 (2002).
170. Soumelis V, Liu YJ. From plasmacytoid to dendritic cell: morphological and functional switches during plasmacytoid pre-dendritic cell differentiation. Eur. J. Immunol. 36, 2286-2292 (2006).
171. Takeuchi S, Furue M. Dendritic cells: ontogeny. Allergol. Int. 56, 215-223 (2007).
172. Villadangos JA, Young L. Antigenpresentation properties of plasmacytoid dendritic cells. Immunity 29, 352-361 (2008).
173. Xiao BG, Huang YM, Link H. Dendritic cell vaccine design: strategies for eliciting peripheral tolerance as therapy of autoimmune diseases. BioDrugs 17, 103-111 (2003).
174. Bergeron A, El-Hage F, Kambouchner M, Lecossier D, Tazi A. Characterisation of dendritic cell subsets in lung cancer micro-environments. Eur. Respir. J. 28, 1170-1177 (2006).
175. Briard D, Azzarone B, Brouty-Boye D. Importance of stromal determinants in the generation of dendritic and natural killer cells in the human spleen. Clin. Exp. Immunol. 140, 265-273 (2005).
176. Cheng P, Nefedova Y, Corzo CA, Gabrilovich DI. Regulation of dendritic-cell differentiation by bone marrow stroma via different Notch ligands. Blood 109, 507-515 (2007).
177. Despars G, Ni K, Bouchard A, O'Neill TJ, O'Neill HC. Molecular definition of an in vitro niche for dendritic cell development. Exp. Hematol. 32, 1182-1193 (2004).
178. Despars G, Periasamy P, Tan J, Abbey J, O'Neill TJ, O'Neill HC. Gene signature of stromal cells which support dendritic cell development. Stem Cells Dev. 17, 917-927 (2008).
179. Despars G, Tan J, Periasamy P, O'Neill HC. The role of stroma in hematopoiesis and dendritic cell development. Curr. Stem Cell Res. Ther. 2, 23-29 (2007). (Pubitemid 46723143)
180. Feuerer M, Beckhove P, Mahnke Y et al. Bone marrow microenvironment facilitating dendritic cell: CD4 T cell interactions and maintenance of CD4 memory. Int. J. Oncol. 25, 867-876 (2004).
181. Glanville SH, Bekiaris V, Jenkinson EJ, Lane PJ, Anderson G, Withers DR. Transplantation of embryonic spleen tissue reveals a role for adult nonlymphoid cells in initiating lymphoid tissue organization. Eur. J. Immunol. 39, 280-289 (2008).
182. Li Q, Guo Z, Xu X, Xia S, Cao X. Pulmonary stromal cells induce the generation of regulatory DC attenuating T-cell-mediated lung inflammation. Eur. J. Immunol. 38, 2751-2761 (2008).
183. O'Neill HC, Jonas N, Wilson H, Ni K. Immunotherapeutic potential of dendritic cells generated in long-term stromadependent cultures. Cancer Biother. Radiopharm. 14, 263-276 (1999). (Pubitemid 29399376)
184. Tan JK, O'Neill HC. Maturation requirements for dendritic cells in T cell stimulation leading to tolerance versus immunity. J. Leukoc. Biol. 78, 319-324 (2005).
185. Xia S, Guo Z, Xu X, Yi H, Wang Q, Cao X. Hepatic microenvironment programs hematopoietic progenitor differentiation into regulatory dendritic cells, maintaining liver tolerance. Blood 112, 3175-3185 (2008).
186. Zhang M, Tang H, Guo Z et al. Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat. Immunol. 5, 1124-1133 (2004).
187. Karnes RJ, Whelan CM, Kwon ED. Immunotherapy for prostate cancer. Curr. Pharm. Des. 12, 807-817 (2006).
188. Kikuchi T. Genetically modified dendritic cells for therapeutic immunity. Tohoku J. Exp. Med. 208, 1-8 (2006).
189. Pinzon-Charry A, Schmidt C, Lopez JA. Dendritic cell immunotherapy for breast cancer. Expert Opin. Biol. Ther. 6, 591-604 (2006).
190. Riker AI, Jove R, Daud AI. Immunotherapy as part of a multidisciplinary approach to melanoma treatment. Front. Biosci. 11, 1-14 (2006).
191. Saito H, Frleta D, Dubsky P, Palucka AK. Dendritic cell-based vaccination against cancer. Hematol. Oncol. Clin. North Am. 20, 689-710 (2006).
192. Xia D, Moyana T, Xiang J. Combinational adenovirus-mediated gene therapy and dendritic cell vaccine in combating well-established tumors. Cell Res. 16, 241-259 (2006).
193. Butterfield LH, Ribas A, Dissette VB et al. A Phase I/II trial testing immunization of hepatocellular carcinoma patients with dendritic cells pulsed with four a-fetoprotein peptides. Clin. Cancer Res. 12, 2817-2825 (2006).
194. Dillman R, Selvan S, Schiltz P et al. Phase I/II trial of melanoma patientspecific vaccine of proliferating autologous tumor cells, dendritic cells, and GM-CSF. planned interim analysis. Cancer Biother. Radiopharm. 19, 658-665 (2004).
195. Hersey P, Menzies SW, Halliday GM et al. Phase I/II study of treatment with dendritic cell vaccines in patients with disseminated melanoma. Cancer Immunol. Immunother. 53, 125-134 (2004).
196. Kyte JA, Mu L, Aamdal S et al. Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumormRNA. Cancer Gene Ther. 13, 905-918 (2006).
197. Lodge PA, Jones LA, Bader RA, Murphy GP, Salgaller ML. Dendritic cell-based immunotherapy of prostate cancer: immune monitoring of a Phase II clinical trial. Cancer Res. 60, 829-833 (2000).
198. Lou E, Marshall J, Aklilu M, Cole D, Chang D, Morse M. A Phase II study of active immunotherapy with PANVAC or autologous, cultured dendritic cells infected with PANVAC after complete resection of hepatic metastases of colorectal carcinoma. Clin. Colorectal Cancer 5, 368-371 (2006).
199. Marten A, Flieger D, Renoth S et al. Therapeutic vaccination against metastatic renal cell carcinoma by autologous dendritic cells: preclinical results and outcome of a first clinical Phase I/II trial. Cancer Immunol. Immunother. 51, 637-644 (2002).
200. Morse MA, Nair SK, Boczkowski D et al. The feasibility and safety of immunotherapy with dendritic cells loaded with CEA mRNA following neoadjuvant chemoradiotherapy and resection of pancreatic cancer. Int. J. Gastrointest. Cancer 32, 1-6 (2002).
201. O'Rourke MG, Johnson M, Lanagan C et al. Durable complete clinical responses in a Phase I/II trial using an autologous melanoma cell/dendritic cell vaccine. Cancer Immunol. Immunother. 52, 387-395 (2003).
202. Pecher G, Haring A, Kaiser L, Thiel E. Mucin gene (MUC1) transfected dendritic cells as vaccine: results of a Phase I/II clinical trial. Cancer Immunol. Immunother. 51, 669-673 (2002).
203. Slingluff CL Jr, Petroni GR, Yamshchikov GV et al. Clinical and immunologic results of a randomized Phase II trial of vaccination using four melanoma peptides either administered in granulocyte-macrophage colony-stimulating factor in adjuvant or pulsed on dendritic cells. J. Clin. Oncol. 21, 4016-4026 (2003).
204. Tjoa BA, Simmons SJ, Bowes VA et al. Evaluation of Phase I/II clinical trials in prostate cancer with dendritic cells and PSMA peptides. Prostate 36, 39-44 (1998).
205. Tjoa BA, Simmons SJ, Elgamal A et al. Follow-up evaluation of a Phase II prostate cancer vaccine trial. Prostate 40, 125-129 (1999). (Pubitemid 29304703)
206. Weihrauch MR, Ansen S, Jurkiewicz E et al. Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer. Clin. Cancer Res. 11, 5993-6001 (2005).
207. Yamanaka R, Abe T, Yajima N et al. Vaccination of recurrent glioma patients with tumour lysate-pulsed dendritic cells elicits immune responses: results of a clinical Phase I/II trial. Br. J. Cancer 89, 1172-1179 (2003).
208. Yamanaka R, Homma J, Yajima N et al. Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical Phase I/II trial. Clin. Cancer Res. 11, 4160-4167 (2005).
209. O'Doherty U, Peng M, Gezelter S et al. Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature. Immunology 82, 487-493 (1994).
210. Grouard G, Rissoan MC, Filgueira L, Durand I, Banchereau J, Liu YJ. The enigmatic plasmacytoid T cells develop into dendritic cells with interleukin (IL)-3 and CD40-ligand. J. Exp. Med. 185, 1101-1111 (1997).
211. Clare-Salzler MJ, Brooks J, Chai A, van Herle K, Anderson C. Prevention of diabetes in nonobese diabetic mice by dendritic cell transfer. J. Clin. Invest. 90, 741-748(1992).
212. Creusot RJ, Yaghoubi SS, Kodama K et al. Tissue-targeted therapy of autoimmune diabetes using dendritic cells transduced to express IL-4 in NOD mice. Clin. Immunol. 127, 176-187 (2008).
213. Feili-Hariri M, Falkner DH, Gambotto A et al. Dendritic cells transduced to express interleukin-4 prevent diabetes in nonobese diabetic mice with advanced insulitis. Hum. Gene Ther. 14, 13-23 (2003).
214. Luo X, Tarbell KV, Yang H et al. Dendritic cells with TGF-b1 differentiate naive CD4+CD25-T cells into islet-protective Foxp3+ regulatory T cells. Proc. Natl Acad. Sci. USA 104, 2821-2826 (2007).
215. Hernandez A, Burger M, Blomberg BB et al. Inhibition of NF-kB during human dendritic cell differentiation generates anergy and regulatory T-cell activity for one but not two human leukocyte antigen DR mismatches. Hum. Immunol. 68, 715-729 (2007).
216. Adorini L, Penna G. Induction of tolerogenic dendritic cells by vitamin D receptor agonists. Handb. Exp. Pharmacol. 251-273 (2009).
217. Adorini L. Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting autoimmune diabetes. Ann. NY Acad. Sci. 987, 258-261 (2003). (Pubitemid 36584031)
218. Besin G, Gaudreau S, Menard M, Guindi C, Dupuis G, Amrani A. Thymic stromal lymphopoietin and thymic stromal lymphopoietin-conditioned dendritic cells induce regulatory T-cell differentiation and protection of NOD mice against diabetes. Diabetes 57, 2107-2117 (2008).
219. Buckland M, Lombardi G. Aspirin and the induction of tolerance by dendritic cells. Handb. Exp. Pharmacol. 188, 197-213 (2009).
220. Kared H, Masson A, Adle-Biassette H, Bach JF, Chatenoud L, Zavala F. Treatment with granulocyte colony-stimulating factor prevents diabetes in NOD mice by recruiting plasmacytoid dendritic cells and functional CD4+CD25+ regulatory T-cells. Diabetes 54, 78-84 (2005).
221. Morin J, Faideau B, Gagnerault MC, Lepault F, Boitard C, Boudaly S. Passive transfer of flt-3L-derived dendritic cells delays diabetes development in NOD mice and associates with early production of interleukin (IL)-4 and IL-10 in the spleen of recipient mice. Handb. Exp. Pharmacol. 134, 388-395 (2003).
222. Papaccio G, Nicoletti F, Pisanti FA, Bendtzen K, Galdieri M. Prevention of spontaneous autoimmune diabetes in NOD mice by transferring in vitro antigen-pulsed syngeneic dendritic cells. Endocrinology 141, 1500-1505 (2000).
223. Steptoe RJ, Ritchie JM, Jones LK, Harrison LC. Autoimmune diabetes is suppressed by transfer of proinsulinencoding Gr-1+ myeloid progenitor cells that differentiate in vivo into resting dendritic cells. Diabetes 54, 434-442 (2005).
224. Menges M, Rossner S, Voigtlander C et al. Repetitive injections of dendritic cells matured with tumor necrosis factor a induce antigen-specific protection of mice from autoimmunity. J. Exp. Med. 195, 15-21 (2002).
225. Verginis P, Li HS, Carayanniotis G. Tolerogenic semimature dendritic cells suppress experimental autoimmune thyroiditis by activation of thyroglobulinspecific CD4+CD25+ T cells. J. Immunol. 174, 7433-7439 (2005).
226. Gangi E, Vasu C, Cheatem D, Prabhakar BS. IL-10-producing CD4+CD25+ regulatory T cells play a critical role in granulocyte-macrophage colonystimulating factor-induced suppression of experimental autoimmune thyroiditis. J. Immunol. 174, 7006-7013 (2005).
227. Chorny A, Gonzalez-Rey E, Fernandez-Martin A, Ganea D, Delgado M. Vasoactive intestinal peptide induces regulatory dendritic cells that prevent acute graft-versus-host disease while maintaining the graft-versus-tumor response. Blood 107, 3787-3794 (2006).
228. Chorny A, Gonzalez-Rey E, Fernandez-Martin A, Pozo D, Ganea D, Delgado M. Vasoactive intestinal peptide induces regulatory dendritic cells with therapeutic effects on autoimmune disorders. Proc. Natl Acad. Sci. USA 102, 13562-13567 (2005).
229. Faunce DE, Terajewicz A, Stein-Streilein J. Cutting edge: in vitrogenerated tolerogenic APC induce CD8+ T regulatory cells that can suppress ongoing experimental autoimmune encephalomyelitis. J. Immunol. 172, 1991-1995 (2004).
230. Zhang Y, Yang H, Xiao B et al. Dendritic cells transduced with lentiviral-mediated RelB-specific ShRNAs inhibit the development of experimental autoimmune myasthenia gravis. Mol. Immunol. 46(4), 657-667 (2008).
231. Kim SH, Kim S, Evans CH, Ghivizzani SC, Oligino T, Robbins PD. Effective treatment of established murine collageninduced arthritis by systemic administration of dendritic cells genetically modified to express IL-4. J. Immunol. 166, 3499-3505 (2001).
232. Kim SH, Lechman ER, Bianco N et al. Exosomes derived from IL-10-treated dendritic cells can suppress inflammation and collagen-induced arthritis. J. Immunol. 174, 6440-6448 (2005).
233. Whalen JD, Thomson AW, Lu L, Robbins PD, Evans CH. Viral IL-10 gene transfer inhibits DTH responses to soluble antigens: evidence for involvement of genetically modified dendritic cells and macrophages. Mol. Ther. 4, 543-550 (2001).
234. Hoves S, Krause SW, Halbritter D et al. Mature but not immature Fas ligand (CD95L)-transduced human monocytederived dendritic cells are protected from Fas-mediated apoptosis and can be used as killer APC. J. Immunol. 170, 5406-5413 (2003).
235. Hoves S, Krause SW, Herfarth H et al. Elimination of activated but not resting primary human CD4+ and CD8+ T cells by Fas ligand (FasL/CD95L)- expressing killerdendritic cells. Immunobiology 208, 463-475 (2004).
236. Torisu M, Murakami H, Akbar F et al. Protective role of interleukin-10-producing regulatory dendritic cells against murine autoimmune gastritis. J. Gastroenterol. 43, 100-107 (2008).
237. Henry E, Desmet CJ, Garze V et al. Dendritic cells genetically engineered to express IL-10 induce long-lasting antigenspecific tolerance in experimental asthma. J. Immunol. 181, 7230-7242 (2008).
238. Wu K, Bi Y, Sun K, Xia J, Wang Y, Wang C. Suppression of allergic inflammation by allergen-DNA-modified dendritic cells depends on the induction of Foxp3+ regulatory T cells. Scand. J. Immunol. 67, 140-151 (2008).
239. Fu F, Li Y, Qian S et al. Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80dim, CD86-) prolong cardiac allograft survival in nonimmunosuppressed recipients. Transplantation 62, 659-665 (1996).
240. Lutz MB, Suri RM, Niimi M et al. 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 (2000).
241. Rastellini C, Lu L, Ricordi C, Starzl TE, Rao AS, Thomson AW. Granulocyte/macrophage colonystimulating factor-stimulated hepatic dendritic cell progenitors prolong pancreatic islet allograft survival. Transplantation 60, 1366-1370 (1995).
242. Sato K, Yamashita N, Yamashita N, Baba M, Matsuyama T. Regulatory dendritic cells protect mice from murine acute graft-versus-host disease and leukemia relapse. Immunity 18, 367-379 (2003).
243. Gregori S, Casorati M, Amuchastegui S, Smiroldo S, Davalli AM, Adorini L. Regulatory T cells induced by 1 a,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J. Immunol. 167, 1945-1953 (2001).
244. Griffin MD, Lutz W, Phan VA, Bachman LA, McKean DJ, Kumar R. Dendritic cell modulation by 1a,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. USA 98, 6800-6805 (2001).
245. Hackstein H, Morelli AE, Larregina AT et al. Aspirin inhibits in vitro maturation and in vivo immunostimulatory function of murine myeloid dendritic cells. J. Immunol. 166, 7053-7062 (2001).
246. Hackstein H, Taner T, Zahorchak AF et al. Rapamycin inhibits IL-4-induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo. Blood 101, 4457-4463 (2003).
247. Hackstein H, Thomson AW. Dendritic cells: emerging pharmacological targets of immunosuppressive drugs. Nat. Rev. Immunol. 4, 24-34 (2004).
248. Lee JI, Ganster RW, Geller DA, Burckart GJ, Thomson AW, Lu L. Cyclosporine A inhibits the expression of costimulatory molecules on in vitrogenerated dendritic cells: association with reduced nuclear translocation of nuclear factor kB. Transplantation 68, 1255-1263 (1999).
249. Ma L, Rudert WA, Harnaha J et al. Immunosuppressive effects of glucosamine. J. Biol. Chem. 277, 39343-39349 (2002).
250. Matasic R, Dietz AB, Vuk-Pavlovic S. Cyclooxygenase-independent inhibition of dendritic cell maturation by aspirin. Immunology 101, 53-60 (2000).
251. Matyszak MK, Citterio S, Rescigno M, Ricciardi-Castagnoli P. Differential effects of corticosteroids during different stages of dendritic cell maturation. Eur. J. Immunol. 30, 1233-1242 (2000).
252. Mehling A, Grabbe S, Voskort M, Schwarz T, Luger TA, Beissert S. Mycophenolate mofetil impairs the maturation and function of murine dendritic cells. J. Immunol. 165, 2374-2381 (2000).
253. Nouri-Shirazi M, Guinet E. Direct and indirect cross-tolerance of alloreactive T cells by dendritic cells retained in the immature stage. Transplantation 74, 1035-1044 (2002).
254. Penna G, Adorini L.1 A,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J. Immunol. 164, 2405-2411 (2000).
255. Piemonti L, Monti P, Allavena P et al. Glucocorticoids affect human dendritic cell differentiation and maturation. J. Immunol. 162, 6473-6481 (1999).
256. Roelen DL, Schuurhuis DH, van den Boogaardt DE et al. Prolongation of skin graft survival by modulation of the alloimmune response with alternatively activated dendritic cells. Transplantation 76, 1608-1615 (2003).
257. Thomas JM, Contreras JL, Jiang XL et al. Peritransplant tolerance induction in macaques: early events reflecting the unique synergy between immunotoxin and deoxyspergualin. Transplantation 68, 1660-1673 (1999).
258. Vosters O, Neve J, De Wit D, Willems F, Goldman M, Verhasselt V. Dendritic cells exposed to nacystelyn are refractory to maturation and promote the emergence of alloreactive regulatory T cells. Transplantation 75, 383-389 (2003).
259. Bonham CA, Peng L, Liang X et al. Marked prolongation of cardiac allograft survival by dendritic cells genetically engineered with NF-k B oligodeoxyribonucleotide decoys and adenoviral vectors encoding CTLA4-Ig. J. Immunol. 169, 3382-3391 (2002).
260. Coates PT, Krishnan R, Kireta S, Johnston J, Russ GR. Human myeloid dendritic cells transduced with an adenoviral interleukin-10 gene construct inhibit human skin graft rejection in humanized NOD-SCID chimeric mice. Gene Ther. 8, 1224-1233 (2001).
261. Gorczynski RM, Bransom J, Cattral M et al. Synergy in induction of increased renal allograft survival after portal vein infusion of dendritic cells transduced to express TGFb and IL-10, along with administration of CHO cells expressing the regulatory molecule OX-2. Clin. Immunol. 95, 182-189 (2000).
262. Lu L, Gambotto A, Lee WC, Qian S, Bonham CA, Robbins PD, Thomson AW. Adenoviral delivery of CTLA4Ig into myeloid dendritic cells promotes their in vitro tolerogenicity and survival in allogeneic recipients. Gene Ther. 6, 554-563 (1999).
263. Min WP, Gorczynski R, Huang XY et al. Dendritic cells genetically engineered to express Fas ligand induce donor-specific hyporesponsiveness and prolong allograft survival. J. Immunol. 164, 161-167 (2000).
264. O'Rourke RW, Kang SM, Lower JA et al. A dendritic cell line genetically modified to express CTLA4-Ig as a means to prolong islet allograft survival. Transplantation 69, 1440-1446 (2000).
265. Takayama T, Morelli AE, Robbins PD, Tahara H, Thomson AW. Feasibility of CTLA4Ig gene delivery and expression in vivo using retrovirally transduced myeloid dendritic cells that induce alloantigen-specific T cell anergy in vitro. Gene Ther. 7, 1265-1273 (2000).
266. Takayama T, Nishioka Y, Lu L, Lotze MT, Tahara H, Thomson AW. Retroviral delivery of viral interleukin-10 into myeloid dendritic cells markedly inhibits their allostimulatory activity and promotes the induction of T-cell hyporesponsiveness. Transplantation 66, 1567-1574 (1998).
267. Terness P, Bauer TM, Rose L, Dufter C, Watzlik A, Simon H, Opelz G. Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites. J. Exp. Med. 196, 447-457 (2002).
268. Garrovillo M, Ali A, Oluwole SF. Indirect allorecognition in acquired thymic tolerance: induction of donor-specific tolerance to rat cardiac allografts by allopeptide-pulsed host dendritic cells. Transplantation 68, 1827-1834 (1999).
269. Kuo YR, Huang CW, Goto S et al. Alloantigen-pulsed host dendritic cells induce T-cell regulation and prolong allograft survival in a rat model of hindlimb allotransplantation. J. Surg. Res. (2008).
270. Taner T, Hackstein H, Wang Z, Morelli AE, Thomson AW. Rapamycintreated, alloantigen-pulsed host dendritic cells induce Ag-specific T cell regulation and prolong graft survival. Am. J. Transplant 5, 228-236 (2005).