CD40/CD154 interactions at the interface of tolerance and immunity

Annual Review of Immunology

Volumn 22, Issue , 2004, Pages 307-328

  Quezada, Sergio A ^a   Jarvinen, Lamis Z ^a   Lind, Evan F ^a   Noelle, Randolph J ^a  

^a DARTMOUTH MEDICAL SCHOOL   (United States)

Author keywords

Cell mediated immunity; Donor transfusion; Immature dendritic cell; Suppressor; Transplantation tolerance

Indexed keywords

CD40 ANTIGEN; CD40 LIGAND;

ALLOGRAFT; ALLOIMMUNITY; ANTIGEN PRESENTING CELL; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CELL MATURATION; CELLULAR IMMUNITY; DENDRITIC CELL; GRAFT REJECTION; HUMAN; IMMUNE RESPONSE; IMMUNITY; IMMUNOLOGICAL TOLERANCE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TRANSPLANTATION TOLERANCE;

ANIMALS; ANTIGENS, CD40; B-LYMPHOCYTES; CD40 LIGAND; CELL COMMUNICATION; DENDRITIC CELLS; HUMANS; IMMUNE TOLERANCE; LYMPHOCYTE ACTIVATION; MODELS, IMMUNOLOGICAL; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 2542476167     PISSN: 07320582     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.immunol.22.012703.104533     Document Type: Review

References (149)

1. van Kooten C, Banchereau J. 1997. Functions of CD40 on B cells, dendritic cells and other cells. Curr. Opin. Immunol. 9:330-37
2. Bourgeois C, Rocha B, Tanchot C. 2002. A role for CD40 expression on CD8+ T cells in the generation of CD8+ T cell memory. Science 297:2060-63
3. Klaus GG, Choi MS, Lam EW, Johnson-Leger C, Cliff J. 1997. CD40: a pivotal receptor in the determination of life/death decisions in B lymphocytes. Int. Rev. Immunol. 15:5-31
4. Higuchi T, Aiba Y, Nomura T, Matsuda J, Mochida K, et al. 2002. Cutting edge: Ectopic expression of CD40 ligand on B cells induces lupus-like autoimmune disease. J. Immunol. 168:9-12
5. Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, et al. 1998. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 391:591-94
6. Danese S, de la Motte C, Sturm A, Vogel JD, West GA, et al. 2003. Platelets trigger a CD40-dependent inflammatory response in the microvasculature of inflammatory bowel disease patients. Gastroenterology 124:1249-64
7. Filion LG, Matusevicius D, Graziani-Bowering GM, Kumar A, Freedman MS. 2003. Monocyte-derived IL12, CD86 (B7-2) and CD40L expression in relapsing and progressive multiple sclerosis. Clin. Immunol. 106:127-38
8. Katsiari CG, Liossis SN, Dimopoulos AM, Charalambopoulo DV, Mavrikakis M, Sfikakis PP. 2002. CD40L overexpression on T cells and monocytes from patients with systemic lupus erythematosus is resistant to calcineurin inhibition. Lupus 11:370-78
9. Schonbeck U, Gerdes N, Varo N, Reynolds RS, Horton DB, et al. 2002. Oxidized low-density lipoprotein augments and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors limit CD40 and CD40L expression in human vascular cells. Circulation 106:2888-93
10. Garside P, Ingulli E, Merica RR, Johnson JG, Noelle RJ, Jenkins MK. 1998. Visualization of specific B and T lymphocyte interactions in the lymph node. Science 281:96-99
11. Jabara H, Laouini D, Tsitsikov E, Mizoguchi E, Bhan A, et al. 2002. The binding site for TRAF2 and TRAF3 but not for TRAF6 is essential for CD40-mediated immunoglobulin class switching. Immunity 17:265-76
12. Ahonen C, Manning E, Erickson LD, O'Connor B, Lind EF, et al. 2002. The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells. Nat. Immunol. 3:451-56
13. Burkly LC. 2001. CD40 pathway blockade as an approach to immunotherapy. Adv. Exp. Med. Biol. 489:135-52
14. Kirk AD, Blair PJ, Tadaki DK, Xu H, Harlan DM. 2001. The role of CD154 in organ transplant rejection and acceptance. Philos. Trans. R. Soc. London Ser. B 356:691-702
15. Markees TG, Phillips NE, Noelle RJ, Shultz LD, Mordes JP, et al. 1997. Prolonged survival of mouse skin allografts in recipients treated with donor splenocytes and antibody to CD40 ligand. Transplantation 64:329-35
16. Vogel LA, Noelle RJ. 1998. CD40 and its crucial role as a member of the TNFR family. Semin. Immunol. 10:435-42
17. Becher B, Durell BG, Miga AV, Hickey WF, Noelle RJ. 2001. The clinical course of experimental autoimmune encephalomyelitis and inflammation is controlled by the expression of CD40 within the central nervous system. J. Exp. Med. 193:967-74
18. Howard LM, Dal Canto MC, Miller SD. 2002. Transient anti-CD154-mediated immunotherapy of ongoing relapsing experimental autoimmune encephalomyelitis induces long-term inhibition of disease relapses. J. Neuroimmunol. 129:58-65
19. Davidson A, Wang X, Mihara M, Ramanujam M, Huang W, et al. 2003. Costimulatory blockade in the treatment of murine systemic lupus erythematosus (SLE). Ann. NY Acad. Sci. 987:188-98
20. Boumpas DT, Furie R, Manzi S, Illei GG, Wallace DJ, et al. 2003. A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis. Arthritis. Rheum. 48:719-27
21. Kalunian KC, Davis JC Jr, Merrill JT, Totoritis MC, Wofsy D. 2002. Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial. Arthritis. Rheum. 46:3251-58
22. Jarvinen LZ, Blazar BR, Adeyi OA, Strom TB, Noelle RJ. 2003. CD154 on the surface of CD4+CD25+ regulatory T cells contributes to skin transplant tolerance. Transplantation 76:In press
23. Gordon EJ, Markees TG, Phillips NE, Noelle RJ, Shultz LD, et al. 1998. Prolonged survival of rat islet and skin xenografts in mice treated with donor splenocytes and anti-CD154 monoclonal antibody. Diabetes 47:1199-206
24. Quezada SA, Fuller B, Jarvinen LZ, Gonzalez M, Blazar BR, et al. 2003. Mechanisms of donor specific transfusion tolerance: preemptive induction of clonal T cell exhaustion via indirect presentation. Blood 102:1920-26
25. Elster EA, Xu H, Tadaki DK, Montgomery S, Burkly LC, et al. 2001. Treatment with the humanized CD154-specific monoclonal antibody, hu5C8, prevents acute rejection of primary skin allografts in nonhuman primates. Transplantation 72:1473-78
26. Benda B, Ljunggren HG, Peach R, Sandberg JO, Korsgren O. 2002. Costimulatory molecules in islet xenotransplantation: CTLA4Ig treatment in CD40 ligand-deficient mice. Cell Transplant. 11:715-20
27. Kurtz J, Ito H, Wekerle T, Shaffer J, Sykes M. 2001. Mechanisms involved in the establishment of tolerance through costimulatory blockade and BMT: lack of requirement for CD40L-mediated signaling for tolerance or deletion of donor-reactive CD4+ cells. Am. J. Transplant. 1:339-49
28. Camirand G, Caron NJ, Turgeon NA, Rossini AA, Tremblay JP. 2002. Treatment with anti-CD154 antibody and donor-specific transfusion prevents acute rejection of myoblast transplantation. Transplantation 73:453-61
29. Tung TH, Mackinnon SE, Mohanakumar T. 2003. Long-term limb allograft survival using anti-CD40L antibody in a murine model. Transplantation 75:644-50
30. Pullen SS, Miller HG, Everdeen DS, Dang TT, Crute JJ, Kehry MR. 1998. CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: regulation of CD40 signaling through multiple TRAF binding sites and TRAF hetero-oligomerization. Biochemistry 37:11836-45
31. Banchereau J, Steinman RM. 1998. Dendritic cells and the control of immunity. Nature 392:245-52
32. Frleta D, Lin JT, Quezada SA, Wade TK, Barth RJ, et al. 2003. Distinctive maturation of in vitro versus in vivo anti-CD40 mAb-matured dendritic cells in mice. J. Immunother. 26:72-84
33. Mackey MF, Wang Z, Eichelberg K, Germain RN. 2003. Distinct contributions of different CD40 TRAF binding sites to CD154-induced dendritic cell maturation and IL-12 secretion. Eur. J. Immunol. 33:779-89
34. Manning E, Pullen SS, Souza DJ, Kehry M, Noelle RJ. 2002. Cellular responses to murine CD40 in a mouse B cell line may be TRAF dependent or independent. Eur. J. Immunol. 32:39-49
35. Wong P, Pamer EG. 2003. Feedback regulation of pathogen-specific T cell priming. Immunity 18:499-511
36. De Smedt T, Pajak B, Klaus GG, Noelle RJ, Urbain J, et al. 1998. Antigen-specific T lymphocytes regulate lipopolysaccharide-induced apoptosis of dendritic cells in vivo. J. Immunol. 161:4476-79
37. Miga AJ, Masters SR, Durell BG, Gonzalez M, Jenkins MK, et al. 2001. Dendritic cell longevity and T cell persistence is controlled by CD154-CD40 interactions. Eur. J. Immunol. 31:959-65
38. Josien R, Li HL, Ingulli E, Sarma S, Wong BR, et al. 2000. TRANCE, a tumor necrosis factor family member, enhances the longevity and adjuvant properties of dendritic cells in vivo. J. Exp. Med. 191:495-502
39. Wong BR, Josien R, Lee SY, Sauter B, Li HL, et al. 1997. TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J. Exp. Med. 186:2075-80
40. Cremer I, Dieu-Nosjean MC, Marechal S, Dezutter-Dambuyant C, Goddard S, et al. 2002. Long-lived immature dendritic cells mediated by TRANCE-RANK interaction. Blood 100:3646-55
41. Ouaaz F, Arron J, Zheng Y, Choi YW, Beg AA. 2002. Dendritic cell development and survival require distinct NF-kappaB subunits. Immunity 16:257-70
42. Ghosh S, Karin M. 2002. Missing pieces in the NF-kappaB puzzle. Cell 109(Suppl.):S81-96
43. Pomerantz JL, Baltimore D. 2002. Two pathways to NF-kappaB. Mol. Cell 10:693-95
44. Grumont R, Hochrein H, O'Keeffe M, Gugasyan R, White C, et al. 2001. c-Rel regulates interleukin 12 p70 expression in CD8(+) dendritic cells by specifically inducing p35 gene transcription. J. Exp. Med. 194:1021-32
45. Yin L, Wu L, Wesche H, Arthur CD, White JM, et al. 2001. Defective lymphotoxin-beta receptor-induced NF-kappaB transcriptional activity in NIK-deficient mice. Science 291:2162-65
46. Kayagaki N, Yan MH, Seshasayee D, Wang H, Lee W, et al. 2002. BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2. Immunity 17:515-24
47. Claudio E, Brown K, Park S, Wang HS, Siebenlist U. 2002. BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells. Nat. Immunol. 3:958-65
48. Saccani S, Pantano S, Natoli G. 2003. Modulation of NF-kappaB activity by exchange of dimers. Mol. Cell 11:1563-74
49. Lind EF, Kosaka Y, Noelle RJ. 2003. The NF-kappa B2 pathway controls dendritic cell longevity and immunity. Submitted
50. Martin E, O'Sullivan B, Low P, Thomas R. 2003. Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10. Immunity 18:155-67
51. Mackey MF, Gunn JR, Maliszewsky C, Kikutani H, Noelle RJ, Barth RJ Jr. 1998. Dendritic cells require maturation via CD40 to generate protective antitumor immunity. J. Immunol. 161:2094-98
52. de Gruijl TD, Luykx-de Bakker SA, Tillman BW, van den Eertwegh AJ, Buter J, et al. 2002. Prolonged maturation and enhanced transduction of dendritic cells migrated from human skin explants after in situ delivery of CD40-targeted adenoviral vectors. J. Immunol. 169:5322-31
53. Morel Y, Truneh A, Sweet RW, Olive D, Costello RT. 2001. The TNF superfamily members LIGHT and CD154 (CD40 ligand) costimulate induction of dendritic cell maturation and elicit specific CTL activity. J. Immunol. 167:2479-86
54. Schulz O, Edwards AD, Schito M, Aliberti J, Manickasingham S, et al. 2000. CD40 triggering of heterodimeric IL-12 p70 production by dendritic cells in vivo requires a microbial priming signal. Immunity 13:453-62
55. Krug A, Towarowski A, Britsch S, Rothenfusser S, Hornung V, et al. 2001. Toll-like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL-12. Eur. J. Immunol. 31:3026-37
56. Bennett SR, Carbone FR, Karamalis F, Flavell RA, Miller JF, Heath WR. 1998. Help for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature 393:478-80
57. Schoenberger SP, Toes RE, van der Voort EI, Offringa R, Melief CJ. 1998. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393:480-83
58. Asea A, Rehli M, Kabingu E, Boch JA, Bare O, et al. 2002. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4. J. Biol. Chem. 277:15028-34
59. Vabulas RM, Ahmad-Nejad P, Ghose S, Kirschning CJ, Issels RD, Wagner H. 2002. HSP70 as endogenous stimulus of the Toll/interleukin-1 receptor signal pathway. J. Biol. Chem. 277:15107-12
60. Vabulas RM, Wagner H, Schild H. 2002. Heat shock proteins as ligands of toll-like receptors. Curr. Top. Microbiol. Immunol. 270:169-84
61. Kedl RM, Jordan M, Potter T, Kappler J, Marrack P, Dow S. 2001. CD40 stimulation accelerates deletion of tumor-specific CD8(+) T cells in the absence of tumor-antigen vaccination. Proc. Natl. Acad. Sci. USA 98:10811-16
62. Mauri C, Mars LT, Londei M. 2000. Therapeutic activity of agonistic monoclonal antibodies against CD40 in a chronic autoimmune inflammatory process. Nat. Med. 6:673-79
63. Janeway CA Jr, Medzhitov R. 1999. Lipoproteins take their toll on the host. Curr. Biol. 9:R879-82
64. Medzhitov R, Janeway C Jr. 2000. The Toll receptor family and microbial recognition. Trends Microbiol. 8:452-56
65. Barton GM, Medzhitov R. 2002. Toll-like receptors and their ligands. Curr. Top. Microbiol. Immunol. 270:81-92
66. Barton GM, Medzhitov R. 2003. Toll-like receptor signaling pathways. Science 300:1524-25
67. Sparwasser T, Koch ES, Vabulas RM, Heeg K, Lipford GB, et al. 1998. Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells. Eur. J. Immunol. 28:2045-54
68. Brunner C, Seiderer J, Schlamp A, Bidlingmaier M, Eigler A, et al. 2000. Enhanced dendritic cell maturation by TNF-alpha or cytidine-phosphate-guanosine DNA drives T cell activation in vitro and therapeutic anti-tumor immune responses in vivo. J. Immunol. 165:6278-86
69. Jakob T, Walker PS, Krieg AM, Udey MC, Vogel JC. 1998. Activation of cutaneous dendritic cells by CpG-containing oligodeoxynucleotides: a role for dendritic cells in the augmentation of Th1 responses by immunostimulatory DNA. J. Immunol. 161:3042-49
70. Melief CJ, Van der Burg SH, Toes RE, Ossendorp F, Offringa R. 2002. Effective therapeutic anticancer vaccines based on precision guiding of cytolytic T lymphocytes. Immunol. Rev. 188:177-82
71. Maxwell JR, Ruby C, Kerkvliet NI, Vella AT. 2002. Contrasting the roles of costimulation and the natural adjuvant lipopolysaccharide during the induction of T cell immunity. J. Immunol. 168: 4372-81
72. Cho HJ, Hayashi T, Datta SK, Takabayashi K, Van Uden JH, et al. 2002. IFN-alpha beta promote priming of antigen-specific CD8+ and CD4+ T lymphocytes by immunostimulatory DNA-based vaccines. J. Immunol. 168:4907-13
73. Gallimore A, Glithero A, Godkin A, Tissot AC, Pluckthun A, et al. 1998. Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes. J. Exp. Med. 187:1383-93
74. Murali-Krishna K, Altman JD, Suresh M, Sourdive DJ, Zajac AJ, et al. 1998. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity 8:177-87
75. De Smedt T, Pajak B, Muraille E, Lespagnard L, Heinen E, et al. 1996. Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo. J. Exp. Med. 184:1413-24
76. Inaba K, Turley S, Iyoda T, Yamaide F, Shimoyama S, et al. 2000. The formation of immunogenic major histocompatibility complex class II-peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli. J. Exp. Med. 191:927-36
77. Noelle RJ. 1996. CD40 and its ligand in host defense. Immunity 4:415-19
78. Karmann K, Hughes CC, Schechner J, Fanslow WC, Pober JS. 1995. CD40 on human endothelial cells: inducibility by cytokines and functional regulation of adhesion molecule expression. Proc. Natl. Acad. Sci. USA 92:4342-46
79. Hollenbaugh D, Mischel-Petty N, Edwards CP, Simon JC, Denfeld RW, et al. 1995. Expression of functional CD40 by vascular endothelial cells. J. Exp. Med. 182:33-40
80. Bouneaud C, Kourilsky P, Bousso P. 2000. Impact of negative selection on the T cell repertoire reactive to a self-peptide: A large fraction of T cell clones escapes clonal deletion. Immunity 13:829-40
81. Gimmi CD, Freeman GJ, Gribben JG, Gray G, Nadler LM. 1993. Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation. Proc. Natl. Acad. Sci. USA 90:6586-90
82. Johnson JG, Jenkins MK. 1993. Accessory cell-derived signals required for T cell activation. Immunol. Res. 12:48-64
83. Steinman RM, Hawiger D, Nussenzweig MC. 2003. Tolerogenic dendritic cells. Annu. Rev. Immunol. 21:685-711
84. Sakaguchi S, Fukuma K, Kuribayashi K, Masuda T. 1985. Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease. J. Exp. Med. 161:72-87
85. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. 1995. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alphachains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155:1151-64
86. Takahashi T, Kuniyasu Y, Toda M, Sakaguchi N, Itoh M, et al. 1998. Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int. Immunol. 10:1969-80
87. Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S. 2002. Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol. 3:135-42
88. Fontenot JD, Gavin MA, Rudensky AY. 2003. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4:330-36
89. Gavin MA, Clarke SR, Negrou E, Gallegos A, Rudensky A. 2002. Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo. Nat. Immunol. 3:33-41
90. Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL. 2002. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 420:502-7
91. Piccirillo CA, Letterio JJ, Thornton AM, McHugh RS, Mamura M, et al. 2002. CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness. J. Exp. Med. 196:237-16
92. Thornton AM, Shevach EM. 1998. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 188:287-96
93. Piccirillo CA, Shevach EM. 2001. Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells. J. Immunol. 167:1137-40
94. Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, et al. 2001. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol. Rev. 182:18-32
95. Sakaguchi S. 2000. Regulatory T cells: key controllers of immunologic self-tolerance. Cell 101:455-58
96. Shevach EM. 2000. Regulatory T cells in autoimmmunity. Annu. Rev. Immunol. 18:423-19
97. Groux H, O'Garra A, Bigler M, Rouleau M, Antonenko S, et al. 1997. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389:737-42
98. Roncarolo MG, Bacchetta R, Bordignon C, Narula S, Levings MK. 2001. Type 1 T regulatory cells. Immunol. Rev. 182:68-79
99. Levings MK, Sangregorio R, Galbiati F, Squadrone S, de Waal Malefyt R, Roncarolo MG. 2001. IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells. J. Immunol. 166:5530-39
100. Bluestone JA, Abbas AK. 2003. Natural versus adaptive regulatory T cells. Nat. Rev. Immunol. 3:253-57
101. Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, et al. 2001. Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 194:769-79
102. Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM. 2002. Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J. Exp. Med. 196:1627-38
103. Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, et al. 2002. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 297:1867-70
104. Steinman RM, Turley S, Mellman I, Inaba K. 2000. The induction of tolerance by dendritic cells that have captured apoptotic cells. J. Exp. Med. 191:411-16
105. Wilson NS, El-Sukkari D, Belz GT, Smith CM, Steptoe RJ, et al. 2003. Most lymphoid organ dendritic cell types are phenotypically and functionally immature. Blood 102:2187-94
106. Scheinecker C, McHugh R, Shevach EM, Germain RN. 2002. Constitutive presentation of a natural tissue autoantigen exclusively by dendritic cells in the draining lymph node. J. Exp. Med. 196:1079-90
107. Mahnke K, Qian Y, Knop J, Enk AH. 2003. Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells. Blood 101:4862-69
108. Albert ML, Sauter B, Bhardwaj N. 1998. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392:86-89
109. 5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J. Exp. Med. 188:1359-68
110. Inaba K, Turley S, Yamaide F, Iyoda T, Mahnke K, et al. 1998. Efficient presentation of phagocytosed cellular fragments on the major histocompatibility complex class II products of dendritic cells. J. Exp. Med. 188:2163-73
111. Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N. 2000. Consequences of cell death: Exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J. Exp. Med. 191:423-34
112. Huynh ML, Fadok VA, Henson PM. 2002. Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J. Clin. Invest. 109:41-50
113. Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RA, Henson PM. 2000. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 405:85-90
114. Kuppner MC, Gastpar R, Gelwer S, Nossner E, Ochmann O, et al. 2001. The role of heat shock protein (hsp70) in dendritic cell maturation: hsp70 induces the maturation of immature dendritic cells but reduces DC differentiation from monocyte precursors. Eur. J. Immunol. 31:1602-9
115. Feng H, Zeng Y, Graner MW, Likhacheva A, Katsanis E. 2003. Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimulate antitumor immunity. Blood 101:245-52
116. Ichikawa HT, Williams LP, Segal BM. 2002. Activation of APCs through CD40 or Toll-like receptor 9 overcomes tolerance and precipitates autoimmune disease. J. Immunol. 169:2781-87
117. Roth E, Schwartzkopff J, Pircher H. 2002. CD40 ligation in the presence of self-reactive CD8 T cells leads to severe immunopathology. J. Immunol. 168:5124-29
118. Diehl L, den Boer AT, Schoenberger SP, van der Voort EI, Schumacher TN, et al. 1999. CD40 activation in vivo overcomes peptide-induced peripheral cytotoxic T-lymphocyte tolerance and augments antitumor vaccine efficacy. Nat. Med. 5:774-79
119. Garza KM, Chan SM, Suri R, Nguyen LT, Odermatt B, et al. 2000. Role of antigen-presenting cells in mediating tolerance and autoimmunity. J. Exp. Med. 191:2021-27
120. Linsley PS, Greene JL, Brady W, Bajorath J, Ledbetter JA, Peach R. 1994. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1:793-801
121. Lenschow DJ, Zeng Y, Thistlethwaite JR, Montag A, Brady W, et al. 1992. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA41g. Science 257:789-92
122. Baliga P, Chavin KD, Qin L, Woodward J, Lin J, et al. 1994. CTLA4Ig prolongs allograft survival while suppressing cell-mediated immunity. Transplantation 58:1082-90
123. Kirk AD, Harlan DM, Armstrong NN, Davis TA, Dong Y, et al. 1997. CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc. Natl. Acad. Sci. USA 94:8789-94
124. Onodera K, Chandraker A, Volk HD, Ritter T, Lehmann M, et al. 1999. Distinct tolerance pathways in sensitized allograft recipients after selective blockade of activation signal 1 or signal 2. Transplantation 68:288-93
125. Zheng XX, Markees TG, Hancock WW, Li Y, Greiner DL, et al. 1999. CTLA4 signals are required to optimally induce allograft tolerance with combined donor-specific transfusion and anti-CD154 monoclonal antibody treatment. J. Immunol. 162:4983-90
126. Markees TG, Phillips NE, Gordon EJ, Noelle RJ, Shultz LD, et al. 1998. 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. 101:2446-55
127. Ranheim EA, Kipps TJ. 1993. Activated T cells induce expression of B7/BB1 on normal or leukemic B cells through a CD40-dependent signal. J. Exp. Med. 177:925-35
128. Ranheim EA, Kipps TJ. 1995. Tumor necrosis factor-alpha facilitates induction of CD80 (B7-1) and CD54 on human B cells by activated T cells: complex regulation by IL-4, IL-10, and CD40L. Cell. Immunol. 161:226-35
129. Jones ND, Van Maurik A, Hara M, Spriewald BM, Witzke O, et al. 2000. CD40-CD40 ligand-independent activation of CD8+ T cells can trigger allograft rejection. J. Immunol. 165:1111-18
130. Lehnert AM, Mottram PL, Han W, Walters SN, Patel AT, et al. 2001. Blockade of the CD28 and CD40 pathways result in the acceptance of pig and rat islet xenografts but not rat cardiac grafts in mice. Transpl. Immunol. 9:51-56
131. Honey K, Cobbold SP, Waldmann H. 1999. CD40 ligand blockade induces CD4+ T cell tolerance and linked suppression. J. Immunol. 163:4805-10
132. Larsen CP, Elwood ET, Alexander DZ, Ritchie SC, Hendrix R, et al. 1996. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 381:434-38
133. Li Y, Zheng XX, Li XC, Zand MS, Strom TB. 1998. Combined costimulation blockade plus rapamycin but not cyclosporine produces permanent engraftment. Transplantation 66:1387-88
134. Li Y, Li XC, Zheng XX, Wells AD, Turka LA, Strom TB. 1999. Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance. Nat. Med. 5:1298-302
135. Li W, Lu L, Wang Z, Wang L, Fung JJ, et al. 2001. Costimulation blockade promotes the apoptotic death of graft-infiltrating T cells and prolongs survival of hepatic allografts from FLT3L-treated donors. Transplantation 72:1423-32
136. Wells AD, Li XC, Li Y, Walsh MC, Zheng XX, et al. 1999. Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance. Nat. Med. 5:1303-7
137. Sho M, Yamada A, Najafian N, Salama AD, Harada H, et al. 2002. Physiological mechanisms of regulating alloimmunity: cytokines, CTLA-4, CD25+ cells, and the alloreactive T cell clone size. J. Immunol. 169:3744-51
138. Brennan DC, Mohanakumar T, Flye MW. 1995. Donor-specific transfusion and donor bone marrow infusion in renal transplantation tolerance: a review of efficacy and mechanisms. Am. J. Kidney Dis. 26:701-15
139. Wood ML, Gottschalk R, Monaco AP. 1984. Comparison of immune responsiveness in mice after single or multiple donor-specific transfusions. J. Immunol. 132:651-55
140. Parker DC, Greiner DL, Phillips NE, Appel MC, Steele AW, et al. 1995. Survival of mouse pancreatic islet allografts in recipients treated with allogeneic small lymphocytes and antibody to CD40 ligand. Proc. Natl. Acad. Sci. USA 92:9560-64
141. Xu H, Montgomery SP, Preston EH, Tadaki DK, Hale DA, et al. 2003. Studies investigating pretransplant donor-specific blood transfusion, rapamycin, and the CD154-specific antibody IDEC-131 in a nonhuman primate model of skin allotransplantation. J. Immunol. 170:2776-82
142. Eynon EE, Parker DC. 1992. Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens. J. Exp. Med. 175:131-38
143. Liu K, Iyoda T, Saternus M, Kimura Y, Inaba K, Steinman RM. 2002. Immune tolerance after delivery of dying cells to dendritic cells in situ. J. Exp. Med. 196:1091-7
144. Coulombe M, Yang H, Wolf LA, Gill RG. 1999. Tolerance to antigen-presenting cell-depleted islet allografts is CD4 T cell dependent. J. Immunol. 162:2503-10
145. Wood KJ, Sakaguchi S. 2003. Regulatory T cells in transplantation tolerance. Nat. Rev. Immunol. 3:199-210
146. Qin S, Cobbold SP, Pope H, Elliott J, Kioussis D, et al. 1993. "Infectious" transplantation tolerance. Science 259:974-77
147. Graca L, Honey K, Adams E, Cobbold SP, Waldmann H. 2000. Cutting edge: anti-CD154 therapeutic antibodies induce infectious transplantation tolerance. J. Immunol. 165:4783-86
148. Hara M, Kingsley CI, Niimi M, Read S, Turvey SE, et al. 2001. IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo. J. Immunol. 166:3789-96
149. Taylor PA, Noelle RJ, Blazar BR. 2001. CD4(+)CD25(+) immune regulatory cells are required for induction of tolerance to alloantigen via costimulatory blockade. J. Exp. Med. 193:1311-18