In vivo induction of regulatory T cells for immune tolerance in hemophilia

Cellular Immunology

Volumn 301, Issue , 2016, Pages 18-29

  Wang, Xiaomei ^a   Terhorst, Cox ^b   Herzog, Roland W ^a  

^a UNIVERSITY OF FLORIDA   (United States)

^b BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

FoxP3; Hemophilia; IL 10; LAP; TGF ; Tr1; Treg

Indexed keywords

ALPHA2 INTEGRIN; BLOOD CLOTTING FACTOR 8; BLOOD CLOTTING FACTOR 9; INTERLEUKIN 10; MAMMALIAN TARGET OF RAPAMYCIN; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; NEUTRALIZING ANTIBODY;

ADOPTIVE TRANSFER; ARTICLE; B LYMPHOCYTE; CD4+ CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CELL EXPANSION; DENDRITIC CELL; ENZYME INHIBITION; EX VIVO STUDY; GENE THERAPY; HEMOPHILIA; HUMAN; IMMUNOLOGICAL TOLERANCE; IN VITRO STUDY; IN VIVO STUDY; MICROENVIRONMENT; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; TH3 CELL; ANIMAL; HEMOPHILIA A; IMMUNOLOGY;

ANIMALS; ANTIBODIES, NEUTRALIZING; FACTOR VIII; HEMOPHILIA A; HUMANS; IMMUNE TOLERANCE; T-LYMPHOCYTES, REGULATORY;

EID: 84959145665     PISSN: 00088749     EISSN: 10902163     Source Type: Journal    
DOI: 10.1016/j.cellimm.2015.10.001     Document Type: Article

References (185)

1. DiMichele D.M. Inhibitor treatment in haemophilias A and B: inhibitor diagnosis. Haemophilia 2006, 12(Suppl. 6):37-41. discussion 41-32.
2. Ghosh K., Shetty S. Immune response to FVIII in hemophilia A: an overview of risk factors. Clin. Rev. Allergy Immunol. 2009, 37:58-66.
3. Ingerslev J., Sorensen B. Parallel use of by-passing agents in haemophilia with inhibitors: a critical review. Br. J. Haematol. 2011, 155:256-262.
4. DiMichele D. Inhibitor development in haemophilia B: an orphan disease in need of attention. Br. J. Haematol. 2007, 138:305-315.
5. Miao C.H. Immunomodulation for inhibitors in hemophilia A: the important role of Treg cells. Expert Rev. Hematol. 2010, 3:469-483.
6. Bluestone J.A., Abbas A.K. Natural versus adaptive regulatory T cells. Nat. Rev. Immunol. 2003, 3:253-257.
7. Sakaguchi S., Wing K., Miyara M. Regulatory T cells - a brief history and perspective. Eur. J. Immunol. 2007, 37(Suppl. 1):S116-S123.
8. Sakaguchi S., Yamaguchi T., Nomura T., Ono M. Regulatory T cells and immune tolerance. Cell 2008, 133:775-787.
9. Frey O., Brauer R. Regulatory T cells: magic bullets for immunotherapy?. Archivum immunologiae et therapiae experimentalis 2006, 54:33-43.
10. Simpson E. Special regulatory T-cell review: regulation of immune responses-examining the role of T cells. Immunology 2008, 123:13-16.
11. Abbas A.K., Benoist C., Bluestone J.A., Campbell D.J., Ghosh S., Hori S., Jiang S., Kuchroo V.K., Mathis D., Roncarolo M.G., Rudensky A., Sakaguchi S., Shevach E.M., Vignali D.A., Ziegler S.F. Regulatory T cells: recommendations to simplify the nomenclature. Nat. Immunol. 2013, 14:307-308.
12. Steinman R.M., Nussenzweig M.C. Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:351-358.
13. Manicassamy S., Pulendran B. Dendritic cell control of tolerogenic responses. Immunol. Rev. 2011, 241:206-227.
14. Pesenacker A.M., Broady R., Levings M.K. Control of tissue-localized immune responses by human regulatory T cells. Eur. J. Immunol. 2015, 45:333-343.
15. Kim Y.C., Zhang A.H., Su Y., Rieder S.A., Rossi R.J., Ettinger R.A., Pratt K.P., Shevach E.M., Scott D.W. Engineered antigen-specific human regulatory T cells: immunosuppression of FVIII-specific T- and B-cell responses. Blood 2015, 125:1107-1115.
16. Cao O., Loduca P.A., Herzog R.W. Role of regulatory T cells in tolerance to coagulation factors. J. Thromb. Haemost. 2009, 7(Suppl. 1):88-91.
17. Scott D.W., Pratt K.P., Miao C.H. Progress toward inducing immunologic tolerance to factor VIII. Blood 2013, 121:4449-4456.
18. Sakaguchi S., Sakaguchi N., Asano M., Itoh M., Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995, 155:1151-1164.
19. Fontenot J.D., Gavin M.A., Rudensky A.Y. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 2003, 4:330-336.
20. Hori S., Nomura T., Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003, 299:1057-1061.
21. Khattri R., Cox T., Yasayko S.A., Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol. 2003, 4:337-342.
22. Groux H., O'Garra A., Bigler M., Rouleau M., Antonenko S., de Vries J.E., Roncarolo M.G. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997, 389:737-742.
23. Weiner H.L. Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol. Rev. 2001, 182:207-214.
24. Anderton S.M., Fillatreau S. Activated B cells in autoimmune diseases: the case for a regulatory role. Nat. Clin. Pract. Rheumatol. 2008, 4:657-666.
25. Fillatreau S., Sweenie C.H., McGeachy M.J., Gray D., Anderton S.M. B cells regulate autoimmunity by provision of IL-10. Nat. Immunol. 2002, 3:944-950.
26. Stockinger B., Barthlott T., Kassiotis G. T cell regulation: a special job or everyone's responsibility?. Nat. Immunol. 2001, 2:757-758.
27. Jonuleit H., Schmitt E., Stassen M., Tuettenberg A., Knop J., Enk A.H. Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood. J. Exp. Med. 2001, 193:1285-1294.
28. Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 2004, 22:531-562.
29. Takahashi T., Tagami T., Yamazaki S., Uede T., Shimizu J., Sakaguchi N., Mak T.W., Sakaguchi S. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 2000, 192:303-310.
30. Shimizu J., Yamazaki S., Takahashi T., Ishida Y., Sakaguchi S. Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol. 2002, 3:135-142.
31. Kuniyasu Y., Takahashi T., Itoh M., Shimizu J., Toda G., Sakaguchi S. Naturally anergic and suppressive CD25(+)CD4(+) T cells as a functionally and phenotypically distinct immunoregulatory T cell subpopulation. Int. Immunol. 2000, 12:1145-1155.
32. Lehmann J., Huehn J., de la Rosa M., Maszyna F., Kretschmer U., Krenn V., Brunner M., Scheffold A., Hamann A. Expression of the integrin alpha Ebeta 7 identifies unique subsets of CD25+ as well as CD25- regulatory T cells. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:13031-13036.
33. Itoh M., Takahashi T., Sakaguchi N., Kuniyasu Y., Shimizu J., Otsuka F., Sakaguchi S. Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J. Immunol. 1999, 162:5317-5326.
34. Walker M.R., Kasprowicz D.J., Gersuk V.H., Benard A., Van Landeghen M., Buckner J.H., Ziegler S.F. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J. Clin. Investig. 2003, 112:1437-1443.
35. Sarrabayrouse G., Bossard C., Chauvin J.M., Jarry A., Meurette G., Quevrain E., Bridonneau C., Preisser L., Asehnoune K., Labarriere N., Altare F., Sokol H., Jotereau F. CD4CD8alphaalpha lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease. PLoS Biol. 2014, 12:e1001833.
36. Nutsch K.M., Hsieh C.S. T cell tolerance and immunity to commensal bacteria. Curr. Opin. Immunol. 2012, 24:385-391.
37. Bennett C.L., Christie J., Ramsdell F., Brunkow M.E., Ferguson P.J., Whitesell L., Kelly T.E., Saulsbury F.T., Chance P.F., Ochs H.D. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 2001, 27:20-21.
38. Williams L.M., Rudensky A.Y. Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat. Immunol. 2007, 8:277-284.
39. Kim J.Y., Kim H.J., Hurt E.M., Chen X., Howard O.M., Farrar W.L. Functional and genomic analyses of FOXP3-transduced Jurkat-T cells as regulatory T (Treg)-like cells. Biochem. Biophys. Res. Commun. 2007, 362:44-50.
40. Fu W., Ergun A., Lu T., Hill J.A., Haxhinasto S., Fassett M.S., Gazit R., Adoro S., Glimcher L., Chan S., Kastner P., Rossi D., Collins J.J., Mathis D., Benoist C. A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells. Nat. Immunol. 2012, 13:972-980.
41. Ohkura N., Hamaguchi M., Morikawa H., Sugimura K., Tanaka A., Ito Y., Osaki M., Tanaka Y., Yamashita R., Nakano N., Huehn J., Fehling H.J., Sparwasser T., Nakai K., Sakaguchi S. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. Immunity 2012, 37:785-799.
42. Tone Y., Furuuchi K., Kojima Y., Tykocinski M.L., Greene M.I., Tone M. Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nat. Immunol. 2008, 9:194-202.
43. Zheng Y., Josefowicz S., Chaudhry A., Peng X.P., Forbush K., Rudensky A.Y. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 2010, 463:808-812.
44. Kim H.P., Leonard W.J. CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation. J. Exp. Med. 2007, 204:1543-1551.
45. Shevach E.M. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 2009, 30:636-645.
46. Collison L.W., Workman C.J., Kuo T.T., Boyd K., Wang Y., Vignali K.M., Cross R., Sehy D., Blumberg R.S., Vignali D.A. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007, 450:566-569.
47. Garin M.I., Chu C.C., Golshayan D., Cernuda-Morollon E., Wait R., Lechler R.I. Galectin-1: a key effector of regulation mediated by CD4+CD25+ T cells. Blood 2007, 109:2058-2065.
48. Tran D.Q., Glass D.D., Uzel G., Darnell D.A., Spalding C., Holland S.M., Shevach E.M. Analysis of adhesion molecules, target cells, and role of IL-2 in human FOXP3+ regulatory T cell suppressor function. J. Immunol. 2009, 182:2929-2938.
49. Gondek D.C., Lu L.F., Quezada S.A., Sakaguchi S., Noelle R.J. Cutting edge: contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J. Immunol. 2005, 174:1783-1786.
50. Grossman W.J., Verbsky J.W., Barchet W., Colonna M., Atkinson J.P., Ley T.J. Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity 2004, 21:589-601.
51. Suri-Payer E., Cantor H. Differential cytokine requirements for regulation of autoimmune gastritis and colitis by CD4(+)CD25(+) T cells. J. Autoimmun. 2001, 16:115-123.
52. McHugh R.S., Whitters M.J., Piccirillo C.A., Young D.A., Shevach E.M., Collins M., Byrne M.C. CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 2002, 16:311-323.
53. Chen M.L., Pittet M.J., Gorelik L., Flavell R.A., Weissleder R., von Boehmer H., Khazaie K. Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc. Natl. Acad. Sci. U.S.A. 2005, 102:419-424.
54. Jordan M.S., Boesteanu A., Reed A.J., Petrone A.L., Holenbeck A.E., Lerman M.A., Naji A., Caton A.J. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2001, 2:301-306.
55. Coutinho A., Caramalho I., Seixas E., Demengeot J. Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive or negative selection. Curr. Top. Microbiol. Immunol. 2005, 293:43-71.
56. Hsieh C.S., Liang Y., Tyznik A.J., Self S.G., Liggitt D., Rudensky A.Y. Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors. Immunity 2004, 21:267-277.
57. Pacholczyk R., Ignatowicz H., Kraj P., Ignatowicz L. Origin and T cell receptor diversity of Foxp3+CD4+CD25+ T cells. Immunity 2006, 25:249-259.
58. Moran A.E., Holzapfel K.L., Xing Y., Cunningham N.R., Maltzman J.S., Punt J., Hogquist K.A. T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J. Exp. Med. 2011, 208:1279-1289.
59. Fontenot J.D., Rasmussen J.P., Gavin M.A., Rudensky A.Y. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat. Immunol. 2005, 6:1142-1151.
60. Burchill M.A., Goetz C.A., Prlic M., O'Neil J.J., Harmon I.R., Bensinger S.J., Turka L.A., Brennan P., Jameson S.C., Farrar M.A. Distinct effects of STAT5 activation on CD4+ and CD8+ T cell homeostasis: development of CD4+CD25+ regulatory T cells versus CD8+ memory T cells. J. Immunol. 2003, 171:5853-5864.
61. Ouyang W., Beckett O., Ma Q., Li M.O. Transforming growth factor-beta signaling curbs thymic negative selection promoting regulatory T cell development. Immunity 2010, 32:642-653.
62. Liu Y., Zhang P., Li J., Kulkarni A.B., Perruche S., Chen W. A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells. Nat. Immunol. 2008, 9:632-640.
63. Atarashi K., Tanoue T., Shima T., Imaoka A., Kuwahara T., Momose Y., Cheng G., Yamasaki S., Saito T., Ohba Y., Taniguchi T., Takeda K., Hori S., Ivanov I.I., Umesaki Y., Itoh K., Honda K. , Induction of colonic regulatory T cells by indigenous Clostridium species. Science 2011, 331:337-341.
64. Lathrop S.K., Bloom S.M., Rao S.M., Nutsch K., Lio C.W., Santacruz N., Peterson D.A., Stappenbeck T.S., Hsieh C.S. Peripheral education of the immune system by colonic commensal microbiota. Nature 2011, 478:250-254.
65. Smith P.M., Howitt M.R., Panikov N., Michaud M., Gallini C.A., Bohlooly Y.M., Glickman J.N., Garrett W.S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013, 341:569-573.
66. Arpaia N., Campbell C., Fan X., Dikiy S., van der Veeken J., deRoos P., Liu H., Cross J.R., Pfeffer K., Coffer P.J., Rudensky A.Y. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 2013, 504:451-455.
67. Coombes J.L., Siddiqui K.R., Arancibia-Carcamo C.V., Hall J., Sun C.M., Belkaid Y., Powrie F. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J. Exp. Med. 2007, 204:1757-1764.
68. Chen Y., Kuchroo V.K., Inobe J., Hafler D.A., Weiner H.L. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 1994, 265:1237-1240.
69. Carrier Y., Yuan J., Kuchroo V.K., Weiner H.L. Th3 cells in peripheral tolerance. I. Induction of Foxp3-positive regulatory T cells by Th3 cells derived from TGF-beta T cell-transgenic mice. J. Immunol. 2007, 178:179-185.
70. Roncarolo M.G., Gregori S., Bacchetta R., Battaglia M. Tr1 cells and the counter-regulation of immunity: natural mechanisms and therapeutic applications. Curr. Top. Microbiol. Immunol. 2014, 380:39-68.
71. Bacchetta R., de Waal Malefijt R., Yssel H., Abrams J., de Vries J.E., Spits H., Roncarolo M.G. Host-reactive CD4+ and CD8+ T cell clones isolated from a human chimera produce IL-5, IL-2, IFN-gamma and granulocyte/macrophage-colony-stimulating factor but not IL-4. J. Immunol. 1990, 144:902-908.
72. Gagliani N., Magnani C.F., Huber S., Gianolini M.E., Pala M., Licona-Limon P., Guo B., Herbert D.R., Bulfone A., Trentini F., Di Serio C., Bacchetta R., Andreani M., Brockmann L., Gregori S., Flavell R.A., Roncarolo M.G. Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nat. Med. 2013, 19:739-746.
73. Brun V., Bastian H., Neveu V., Foussat A. Clinical grade production of IL-10 producing regulatory Tr1 lymphocytes for cell therapy of chronic inflammatory diseases. Int. Immunopharmacol. 2009, 9:609-613.
74. Vieira P.L., Christensen J.R., Minaee S., O'Neill E.J., Barrat F.J., Boonstra A., Barthlott T., Stockinger B., Wraith D.C., O'Garra A. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J. Immunol. 2004, 172:5986-5993.
75. Levings M.K., Gregori S., Tresoldi E., Cazzaniga S., Bonini C., Roncarolo M.G. Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood 2005, 105:1162-1169.
76. Yamanaka K., Yuta A., Kakeda M., Sasaki R., Kitagawa H., Gabazza E.C., Okubo K., Kurokawa I., Mizutani H. Induction of IL-10-producing regulatory T cells with TCR diversity by epitope-specific immunotherapy in pollinosis. J. Allergy Clin. Immunol. 2009, 124:842-845. e847.
77. Taga K., Tosato G. IL-10 inhibits human T cell proliferation and IL-2 production. J. Immunol. 1992, 148:1143-1148.
78. Gorelik L., Flavell R.A. Transforming growth factor-beta in T-cell biology. Nat. Rev. Immunol. 2002, 2:46-53.
79. de Waal Malefyt R., Haanen J., Spits H., Roncarolo M.G., te Velde A., Figdor C., Johnson K., Kastelein R., Yssel H., De Vries J.E. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J. Exp. Med. 1991, 174:915-924.
80. Fiorentino D.F., Zlotnik A., Mosmann T.R., Howard M., O'Garra A. IL-10 inhibits cytokine production by activated macrophages. J. Immunol. 1991, 147:3815-3822.
81. Roncarolo M.G., Gregori S., Battaglia M., Bacchetta R., Fleischhauer K., Levings M.K. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol. Rev. 2006, 212:28-50.
82. Morelli A.E., Thomson A.W. Tolerogenic dendritic cells and the quest for transplant tolerance. Nat. Rev. Immunol. 2007, 7:610-621.
83. Satoguina J.S., Weyand E., Larbi J., Hoerauf A. T regulatory-1 cells induce IgG4 production by B cells: role of IL-10. J. Immunol. 2005, 174:4718-4726.
84. Meiler F., Zumkehr J., Klunker S., Ruckert B., Akdis C.A., Akdis M. In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure. J. Exp. Med. 2008, 205:2887-2898.
85. Haringer B., Lozza L., Steckel B., Geginat J. Identification and characterization of IL-10/IFN-gamma-producing effector-like T cells with regulatory function in human blood. J. Exp. Med. 2009, 206:1009-1017.
86. Bacchetta R., Sartirana C., Levings M.K., Bordignon C., Narula S., Roncarolo M.G. Growth and expansion of human T regulatory type 1 cells are independent from TCR activation but require exogenous cytokines. Eur. J. Immunol. 2002, 32:2237-2245.
87. Mandapathil M., Szczepanski M.J., Szajnik M., Ren J., Jackson E.K., Johnson J.T., Gorelik E., Lang S., Whiteside T.L. Adenosine and prostaglandin E2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cells. J. Biol. Chem. 2010, 285:27571-27580.
88. Grossman W.J., Verbsky J.W., Tollefsen B.L., Kemper C., Atkinson J.P., Ley T.J. Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells. Blood 2004, 104:2840-2848.
89. Magnani C.F., Alberigo G., Bacchetta R., Serafini G., Andreani M., Roncarolo M.G., Gregori S. Killing of myeloid APCs via HLA class I, CD2 and CD226 defines a novel mechanism of suppression by human Tr1 cells. Eur. J. Immunol. 2011, 41:1652-1662.
90. Pot C., Jin H., Awasthi A., Liu S.M., Lai C.Y., Madan R., Sharpe A.H., Karp C.L., Miaw S.C., Ho I.C., Kuchroo V.K. Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells. J. Immunol. 2009, 183:797-801.
91. Gregori S., Tomasoni D., Pacciani V., Scirpoli M., Battaglia M., Magnani C.F., Hauben E., Roncarolo M.G. Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway. Blood 2010, 116:935-944.
92. Murugaiyan G., Mittal A., Lopez-Diego R., Maier L.M., Anderson D.E., Weiner H.L. IL-27 is a key regulator of IL-10 and IL-17 production by human CD4+ T cells. J. Immunol. 2009, 183:2435-2443.
93. Iyer S.S., Ghaffari A.A., Cheng G. Lipopolysaccharide-mediated IL-10 transcriptional regulation requires sequential induction of type I IFNs and IL-27 in macrophages. J. Immunol. 2010, 185:6599-6607.
94. Zhang X., Huang H., Yuan J., Sun D., Hou W.S., Gordon J., Xiang J. CD4-8- dendritic cells prime CD4+ T regulatory 1 cells to suppress antitumor immunity. J. Immunol. 2005, 175:2931-2937.
95. Steinman R.M., Hawiger D., Liu K., Bonifaz L., Bonnyay D., Mahnke K., Iyoda T., Ravetch J., Dhodapkar M., Inaba K., Nussenzweig M. Dendritic cell function in vivo during the steady state: a role in peripheral tolerance. Ann. N.Y. Acad. Sci. 2003, 987:15-25.
96. Battaglia M., Stabilini A., Roncarolo M.G. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood 2005, 105:4743-4748.
97. Wang Y., Camirand G., Lin Y., Froicu M., Deng S., Shlomchik W.D., Lakkis F.G., Rothstein D.M. Regulatory T cells require mammalian target of rapamycin signaling to maintain both homeostasis and alloantigen-driven proliferation in lymphocyte-replete mice. J. Immunol. 2011, 186:2809-2818.
98. Lu L., Qian X.F., Rao J.H., Wang X.H., Zheng S.G., Zhang F. Rapamycin promotes the expansion of CD4(+) Foxp3(+) regulatory T cells after liver transplantation. Transpl. Proc. 2010, 42:1755-1757.
99. Strauss L., Czystowska M., Szajnik M., Mandapathil M., Whiteside T.L. Differential responses of human regulatory T cells (Treg) and effector T cells to rapamycin. PLoS One 2009, 4:e5994.
100. Liu Y., Chen Y., Liu F.Q., Lamb J.R., Tam P.K. Combined treatment with triptolide and rapamycin prolongs graft survival in a mouse model of cardiac transplantation. Transplant Int. 2008, 21:483-494.
101. Zhang W., Zhang D., Shen M., Liu Y., Tian Y., Thomson A.W., Lee W.P., Zheng X.X. Combined administration of a mutant TGF-beta1/Fc and rapamycin promotes induction of regulatory T cells and islet allograft tolerance. J. Immunol. 2010, 185:4750-4759.
102. Gagliani N., Gregori S., Jofra T., Valle A., Stabilini A., Rothstein D.M., Atkinson M., Roncarolo M.G., Battaglia M. Rapamycin combined with anti-CD45RB mAb and IL-10 or with G-CSF induces tolerance in a stringent mouse model of islet transplantation. PLoS One 2011, 6:e28434.
103. Delgoffe G.M., Pollizzi K.N., Waickman A.T., Heikamp E., Meyers D.J., Horton M.R., Xiao B., Worley P.F., Powell J.D. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat. Immunol. 2011, 12:295-303.
104. Moghimi B., Sack B.K., Nayak S., Markusic D.M., Mah C.S., Herzog R.W. Induction of tolerance to factor VIII by transient co-administration with rapamycin. J. Thromb. Haemost. 2011, 9:1524-1533.
105. Nayak S., Cao O., Hoffman B.E., Cooper M., Zhou S., Atkinson M.A., Herzog R.W. Prophylactic immune tolerance induced by changing the ratio of antigen-specific effector to regulatory T cells. J. Thromb. Haemost. 2009, 7:1523-1532.
106. Nayak S., Sarkar D., Perrin G.Q., Moghimi B., Hoffman B.E., Zhou S., Byrne B.J., Herzog R.W. Prevention and reversal of antibody responses against factor IX in gene therapy for hemophilia B. Front. Microbiol. 2011, 2:244.
107. Miao C.H., Ye P., Thompson A.R., Rawlings D.J., Ochs H.D. Immunomodulation of transgene responses following naked DNA transfer of human factor VIII into hemophilia A mice. Blood 2006, 108:19-27.
108. Maldonado R.A., LaMothe R.A., Ferrari J.D., Zhang A.H., Rossi R.J., Kolte P.N., Griset A.P., O'Neil C., Altreuter D.H., Browning E., Johnston L., Farokhzad O.C., Langer R., Scott D.W., von Andrian U.H., Kishimoto T.K. Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance. Proc. Natl. Acad. Sci. U.S.A. 2015, 112:E156-E165.
109. McKenna H.J., Stocking K.L., Miller R.E., Brasel K., De Smedt T., Maraskovsky E., Maliszewski C.R., Lynch D.H., Smith J., Pulendran B., Roux E.R., Teepe M., Lyman S.D., Peschon J.J. Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood 2000, 95:3489-3497.
110. Waskow C., Liu K., Darrasse-Jeze G., Guermonprez P., Ginhoux F., Merad M., Shengelia T., Yao K., Nussenzweig M. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat. Immunol. 2008, 9:676-683.
111. Kingston D., Schmid M.A., Onai N., Obata-Onai A., Baumjohann D., Manz M.G. The concerted action of GM-CSF and Flt3-ligand on in vivo dendritic cell homeostasis. Blood 2009, 114:835-843.
112. Laouar Y., Welte T., Fu X.Y., Flavell R.A. STAT3 is required for Flt3L-dependent dendritic cell differentiation. Immunity 2003, 19:903-912.
113. Hoentjen F., Sartor R.B., Ozaki M., Jobin C. STAT3 regulates NF-kappaB recruitment to the IL-12p40 promoter in dendritic cells. Blood 2005, 105:689-696.
114. Kitamura H., Kamon H., Sawa S., Park S.J., Katunuma N., Ishihara K., Murakami M., Hirano T. IL-6-STAT3 controls intracellular MHC class II alphabeta dimer level through cathepsin S activity in dendritic cells. Immunity 2005, 23:491-502.
115. Svensson M.N., Andersson S.E., Erlandsson M.C., Jonsson I.M., Ekwall A.K., Andersson K.M., Nilsson A., Bian L., Brisslert M., Bokarewa M.I. Fms-like tyrosine kinase 3 ligand controls formation of regulatory T cells in autoimmune arthritis. PLoS One 2013, 8:e54884.
116. Klein O., Ebert L.M., Zanker D., Woods K., Tan B.S., Fucikova J., Behren A., Davis I.D., Maraskovsky E., Chen W., Cebon J. Flt3 ligand expands CD4+ FoxP3+ regulatory T cells in human subjects. Eur. J. Immunol. 2013, 43:533-539.
117. Shao Z., Bharadwaj A.S., McGee H.S., Makinde T.O., Agrawal D.K. Fms-like tyrosine kinase 3 ligand increases a lung DC subset with regulatory properties in allergic airway inflammation. J. Allergy Clin. Immunol. 2009, 123:917-924. e912.
118. Kool M., van Nimwegen M., Willart M.A., Muskens F., Boon L., Smit J.J., Coyle A., Clausen B.E., Hoogsteden H.C., Lambrecht B.N., Hammad H. An anti-inflammatory role for plasmacytoid dendritic cells in allergic airway inflammation. J. Immunol. 2009, 183:1074-1082.
119. Collins C.B., Aherne C.M., McNamee E.N., Lebsack M.D., Eltzschig H., Jedlicka P., Rivera-Nieves J. Flt3 ligand expands CD103(+) dendritic cells and FoxP3(+) T regulatory cells, and attenuates Crohn's-like murine ileitis. Gut 2012, 61:1154-1162.
120. Choi J.H., Cheong C., Dandamudi D.B., Park C.G., Rodriguez A., Mehandru S., Velinzon K., Jung I.H., Yoo J.Y., Oh G.T., Steinman R.M. Flt3 signaling-dependent dendritic cells protect against atherosclerosis. Immunity 2011, 35:819-831.
121. Biswas M., Sarkar D., Kumar S.R., Nayak S., Rogers G.L., Markusic D.M., Liao G., Terhorst C., Herzog R.W. Synergy between rapamycin and FLT3 ligand enhances plasmacytoid dendritic cell-dependent induction of CD4+CD25+FoxP3+ Treg. Blood 2015, 125:2937-2947.
122. Peng B., Ye P., Blazar B.R., Freeman G.J., Rawlings D.J., Ochs H.D., Miao C.H. Transient blockade of the inducible costimulator pathway generates long-term tolerance to factor VIII after nonviral gene transfer into hemophilia A mice. Blood 2008, 112:1662-1672.
123. Hausl C., Ahmad R.U., Schwarz H.P., Muchitsch E.M., Turecek P.L., Dorner F., Reipert B.M. Preventing restimulation of memory B cells in hemophilia A: a potential new strategy for the treatment of antibody-dependent immune disorders. Blood 2004, 104:115-122.
124. Qian J., Collins M., Sharpe A.H., Hoyer L.W. Prevention and treatment of factor VIII inhibitors in murine hemophilia A. Blood 2000, 95:1324-1329.
125. Reipert B.M., Sasgary M., Ahmad R.U., Auer W., Turecek P.L., Schwarz H.P. Blockade of CD40/CD40 ligand interactions prevents induction of factor VIII inhibitors in hemophilic mice but does not induce lasting immune tolerance. Thromb. Haemost. 2001, 86:1345-1352.
126. Rossi G., Sarkar J., Scandella D. Long-term induction of immune tolerance after blockade of CD40-CD40L interaction in a mouse model of hemophilia A. Blood 2001, 97:2750-2757.
127. Liu C.L., Ye P., Lin J., Djukovic D., Miao C.H. Long-term tolerance to factor VIII is achieved by administration of interleukin-2/interleukin-2 monoclonal antibody complexes and low dosages of factor VIII. J. Thromb. Haemost. 2014, 12:921-931.
128. Liu C.L., Ye P., Yen B.C., Miao C.H. In vivo expansion of regulatory T cells with IL-2/IL-2 mAb complexes prevents anti-factor VIII immune responses in hemophilia A mice treated with factor VIII plasmid-mediated gene therapy. Mol. Ther. 2011, 19:1511-1520.
129. Liao G., Nayak S., Regueiro J.R., Berger S.B., Detre C., Romero X., de Waal Malefyt R., Chatila T.A., Herzog R.W., Terhorst C. GITR engagement preferentially enhances proliferation of functionally competent CD4+CD25+FoxP3+ regulatory T cells. Int. Immunol. 2010, 22:259-270.
130. Waters B., Qadura M., Burnett E., Chegeni R., Labelle A., Thompson P., Hough C., Lillicrap D. Anti-CD3 prevents factor VIII inhibitor development in hemophilia A mice by a regulatory CD4+CD25+-dependent mechanism and by shifting cytokine production to favor a Th1 response. Blood 2009, 113:193-203.
131. Peng B., Ye P., Rawlings D.J., Ochs H.D., Miao C.H. Anti-CD3 antibodies modulate anti-factor VIII immune responses in hemophilia A mice after factor VIII plasmid-mediated gene therapy. Blood 2009, 114:4373-4382.
132. Valle A., Barbagiovanni G., Jofra T., Stabilini A., Perol L., Baeyens A., Anand S., Cagnard N., Gagliani N., Piaggio E., Battaglia M. Heterogeneous CD3 expression levels in differing T cell subsets correlate with the in vivo anti-CD3-mediated T cell modulation. J. Immunol. 2015, 194:2117-2127.
133. Lei T.C., Scott D.W. Induction of tolerance to factor VIII inhibitors by gene therapy with immunodominant A2 and C2 domains presented by B cells as Ig fusion proteins. Blood 2005, 105:4865-4870.
134. Wang X., Moghimi B., Zolotukhin I., Morel L.M., Cao O., Herzog R.W. Immune tolerance induction to factor IX through B cell gene transfer: TLR9 signaling delineates between tolerogenic and immunogenic B cells. Mol. Ther. 2014, 22:1139-1150.
135. Skupsky J., Su Y., Lei T.C., Scott D.W. Tolerance induction by gene transfer to lymphocytes. Curr. Gene Ther. 2007, 7:369-380.
136. Cousens L.P., Najafian N., Mingozzi F., Elyaman W., Mazer B., Moise L., Messitt T.J., Su Y., Sayegh M., High K., Khoury S.J., Scott D.W., De Groot A.S. In vitro and in vivo studies of IgG-derived Treg epitopes (Tregitopes): a promising new tool for tolerance induction and treatment of autoimmunity. J. Clin. Immunol. 2013, 33(Suppl. 1):S43-S49.
137. Ahangarani R.R., Janssens W., Carlier V., Vanderelst L., Vandendriessche T., Chuah M., Jacquemin M., Saint-Remy J.M. Retroviral vectors induce epigenetic chromatin modifications and IL-10 production in transduced B cells via activation of toll-like receptor 2. Mol. Ther. 2011, 19:711-722.
138. Su Y., Zhang A.H., Noben-Trauth N., Scott D.W. B-cell gene therapy for tolerance induction: host but not donor B-cell derived IL-10 is necessary for tolerance. Front. Microbiol. 2011, 2:154.
139. Tran C.A., Burton L., Russom D., Wagner J.R., Jensen M.C., Forman S.J., DiGiusto D.L. Manufacturing of large numbers of patient-specific T cells for adoptive immunotherapy: an approach to improving product safety, composition, and production capacity. J. Immunother. 2007, 30:644-654.
140. Roncarolo M.G., Battaglia M. Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans. Nat. Rev. Immunol. 2007, 7:585-598.
141. Tang Q., Henriksen K.J., Bi M., Finger E.B., Szot G., Ye J., Masteller E.L., McDevitt H., Bonyhadi M., Bluestone J.A. In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J. Exp. Med. 2004, 199:1455-1465.
142. Sarkar D., Biswas M., Liao G., Seay H.R., Perrin G.Q., Markusic D.M., Hoffman B.E., Brusko T.M., Terhorst C., Herzog R.W. Expanded autologous polyclonal regulatory T Cells suppress inhibitor formation in hemophilia. Mol. Ther. Methods Clin. Dev. 2014, 1.
143. Miao C.H., Harmeling B.R., Ziegler S.F., Yen B.C., Torgerson T., Chen L., Yau R.J., Peng B., Thompson A.R., Ochs H.D., Rawlings D.J. CD4+FOXP3+ regulatory T cells confer long-term regulation of factor VIII-specific immune responses in plasmid-mediated gene therapy-treated hemophilia mice. Blood 2009, 114:4034-4044.
144. Madoiwa S., Yamauchi T., Kobayashi E., Hakamata Y., Dokai M., Makino N., Kashiwakura Y., Ishiwata A., Ohmori T., Mimuro J., Sakata Y. Induction of factor VIII-specific unresponsiveness by intrathymic factor VIII injection in murine hemophilia A. J. Thromb. Haemost. 2009, 7:811-824.
145. Marodon G., Fisson S., Levacher B., Fabre M., Salomon B.L., Klatzmann D. Induction of antigen-specific tolerance by intrathymic injection of lentiviral vectors. Blood 2006, 108:2972-2978.
146. Coleman M.A., Steptoe R.J. Induction of antigen-specific tolerance through hematopoietic stem cell-mediated gene therapy: the future for therapy of autoimmune disease?. Autoimmun. Rev. 2012, 12:195-203.
147. Elinav E., Adam N., Waks T., Eshhar Z. Amelioration of colitis by genetically engineered murine regulatory T cells redirected by antigen-specific chimeric receptor. Gastroenterology 2009, 136:1721-1731.
148. Fransson M., Piras E., Burman J., Nilsson B., Essand M., Lu B., Harris R.A., Magnusson P.U., Brittebo E., Loskog A.S. CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery. J. Neuroinflammation 2012, 9:112.
149. Crispe I.N. Hepatic T cells and liver tolerance. Nat. Rev. Immunol. 2003, 3:51-62.
150. Rogers G.L., Martino A.T., Aslanidi G.V., Jayandharan G.R., Srivastava A., Herzog R.W. Innate immune responses to AAV vectors. Front. Microbiol. 2011, 2:194.
151. Cao O., Dobrzynski E., Wang L., Nayak S., Mingle B., Terhorst C., Herzog R.W. Induction and role of regulatory CD4+CD25+ T cells in tolerance to the transgene product following hepatic in vivo gene transfer. Blood 2007, 110:1132-1140.
152. Cooper M., Nayak S., Hoffman B.E., Terhorst C., Cao O., Herzog R.W. Improved induction of immune tolerance to factor IX by hepatic AAV-8 gene transfer. Hum. Gene Ther. 2009, 20:767-776.
153. Markusic D.M., Hoffman B.E., Perrin G.Q., Nayak S., Wang X., LoDuca P.A., High K.A., Herzog R.W. Effective gene therapy for haemophilic mice with pathogenic factor IX antibodies. EMBO Mol. Med. 2013, 5:1698-1709.
154. Sack B.K., Herzog R.W., Terhorst C., Markusic D.M. Development of gene transfer for induction of antigen-specific tolerance. Mol. Ther. 2014, 1:14013.
155. Mingozzi F., Liu Y.L., Dobrzynski E., Kaufhold A., Liu J.H., Wang Y., Arruda V.R., High K.A., Herzog R.W. Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer. J. Clin. Investig. 2003, 111:1347-1356.
156. Hoffman B.E., Martino A.T., Sack B.K., Cao O., Liao G., Terhorst C., Herzog R.W. Nonredundant roles of IL-10 and TGF-beta in suppression of immune responses to hepatic AAV-factor IX gene transfer. Mol. Ther. 2011, 19:1263-1272.
157. Liao G., van Driel B., Magelky E., O'Keeffe M.S., de Waal Malefyt R., Engel P., Herzog R.W., Mizoguchi E., Bhan A.K., Terhorst C. Glucocorticoid-induced TNF receptor family-related protein ligand regulates the migration of monocytes to the inflamed intestine. FASEB J. 2014, 28:474-484.
158. Breous E., Somanathan S., Vandenberghe L.H., Wilson J.M. Hepatic regulatory T cells and Kupffer cells are crucial mediators of systemic T cell tolerance to antigens targeting murine liver. Hepatology 2009, 50:612-621.
159. Dobrzynski E., Mingozzi F., Liu Y.L., Bendo E., Cao O., Wang L., Herzog R.W. Induction of antigen-specific CD4+ T-cell anergy and deletion by in vivo viral gene transfer. Blood 2004, 104:969-977.
160. Faust S.M., Bell P., Zhu Y., Sanmiguel J., Wilson J.M. The role of apoptosis in immune hyporesponsiveness following AAV8 liver gene transfer. Mol. Ther. 2013, 21:2227-2235.
161. Finn J.D., Ozelo M.C., Sabatino D.E., Franck H.W., Merricks E.P., Crudele J.M., Zhou S., Kazazian H.H., Lillicrap D., Nichols T.C., Arruda V.R. Eradication of neutralizing antibodies to factor VIII in canine hemophilia A after liver gene therapy. Blood 2010, 116:5842-5848.
162. Annoni A., Cantore A., Della Valle P., Goudy K., Akbarpour M., Russo F., Bartolaccini S., D'Angelo A., Roncarolo M.G., Naldini L. Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice. EMBO Mol. Med. 2013, 5:1684-1697.
163. Crudele J.M., Finn J.D., Siner J.I., Martin N.B., Niemeyer G.P., Zhou S., Mingozzi F., Lothrop C.D., Arruda V.R. AAV liver expression of FIX-Padua prevents and eradicates FIX inhibitor without increasing thrombogenicity in hemophilia B dogs and mice. Blood 2015, 125:1553-1561.
164. Sack B.K., Merchant S., Markusic D.M., Nathwani A.C., Davidoff A.M., Byrne B.J., Herzog R.W. Transient B cell depletion or improved transgene expression by codon optimization promote tolerance to factor VIII in gene therapy. PLoS One 2012, 7:e37671.
165. Weiner H.L., da Cunha A.P., Quintana F., Wu H. Oral tolerance. Immunol. Rev. 2011, 241:241-259.
166. Wang X., Sherman A., Liao G., Leong K.W., Daniell H., Terhorst C., Herzog R.W. Mechanism of oral tolerance induction to therapeutic proteins. Adv. Drug Deliv. Rev. 2013, 65:759-773.
167. Miller A., Lider O., Roberts A.B., Sporn M.B., Weiner H.L. Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. Proc. Natl. Acad. Sci. U.S.A. 1992, 89:421-425.
168. Faria A.M., Weiner H.L. Oral tolerance. Immunol. Rev. 2005, 206:232-259.
169. Wahl S.M., Wen J., Moutsopoulos N. TGF-beta: a mobile purveyor of immune privilege. Immunol. Rev. 2006, 213:213-227.
170. Li M.O., Wan Y.Y., Flavell R.A. T cell-produced transforming growth factor-beta1 controls T cell tolerance and regulates Th1- and Th17-cell differentiation. Immunity 2007, 26:579-591.
171. Mucida D., Kutchukhidze N., Erazo A., Russo M., Lafaille J.J., Curotto de Lafaille M.A. Oral tolerance in the absence of naturally occurring Tregs. J. Clin. Investig. 2005, 115:1923-1933.
172. McKarns S.C., Schwartz R.H., Kaminski N.E. Smad3 is essential for TGF-beta 1 to suppress IL-2 production and TCR-induced proliferation, but not IL-2-induced proliferation. J. Immunol. 2004, 172:4275-4284.
173. Heath V.L., Murphy E.E., Crain C., Tomlinson M.G., O'Garra A. TGF-beta1 down-regulates Th2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression. Eur. J. Immunol. 2000, 30:2639-2649.
174. Neurath M.F., Weigmann B., Finotto S., Glickman J., Nieuwenhuis E., Iijima H., Mizoguchi A., Mizoguchi E., Mudter J., Galle P.R., Bhan A., Autschbach F., Sullivan B.M., Szabo S.J., Glimcher L.H., Blumberg R.S. The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. J. Exp. Med. 2002, 195:1129-1143.
175. Hyytiainen M., Penttinen C., Keski-Oja J. Latent TGF-beta binding proteins: extracellular matrix association and roles in TGF-beta activation. Crit. Rev. Clin. Lab. Sci. 2004, 41:233-264.
176. Lacy-Hulbert A., Smith A.M., Tissire H., Barry M., Crowley D., Bronson R.T., Roes J.T., Savill J.S., Hynes R.O. Ulcerative colitis and autoimmunity induced by loss of myeloid alphav integrins. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:15823-15828.
177. Travis M.A., Reizis B., Melton A.C., Masteller E., Tang Q., Proctor J.M., Wang Y., Bernstein X., Huang X., Reichardt L.F., Bluestone J.A., Sheppard D. Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. Nature 2007, 449:361-365.
178. Oida T., Weiner H.L. TGF-beta induces surface LAP expression on murine CD4 T cells independent of Foxp3 induction. PLoS One 2010, 5:e15523.
179. Ochi H., Abraham M., Ishikawa H., Frenkel D., Yang K., Basso A., Wu H., Chen M.L., Gandhi R., Miller A., Maron R., Weiner H.L. New immunosuppressive approaches: oral administration of CD3-specific antibody to treat autoimmunity. J. Neurol. Sci. 2008, 274:9-12.
180. Zhang X., Reddy J., Ochi H., Frenkel D., Kuchroo V.K., Weiner H.L. Recovery from experimental allergic encephalomyelitis is TGF-beta dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T cells. Int. Immunol. 2006, 18:495-503.
181. Kwon K.C., Verma D., Singh N.D., Herzog R., Daniell H. Oral delivery of human biopharmaceuticals, autoantigens and vaccine antigens bioencapsulated in plant cells. Adv. Drug Deliv. Rev. 2013, 65:782-799.
182. Verma D., Moghimi B., LoDuca P.A., Singh H.D., Hoffman B.E., Herzog R.W., Daniell H. Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:7101-7106.
183. Wang X., Su J., Sherman A., Rogers G.L., Liao G., Hoffman B.E., Leong K.W., Terhorst C., Daniell H., Herzog R.W. Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells. Blood 2015, 125:2418-2427.
184. Sherman A., Su J., Lin S., Wang X., Herzog R.W., Daniell H. Suppression of inhibitor formation against FVIII in a murine model of hemophilia A by oral delivery of antigens bioencapsulated in plant cells. Blood 2014, 124:1659-1668.
185. Su J., Zhu L., Sherman A., Wang X., Lin S., Kamesh A., Norikane J.H., Streatfield S.J., Herzog R.W., Daniell H. Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B. Biomaterials 2015, 70:84-93.