Regulatory T-cell therapy for inflammatory bowel disease: More questions than answers

Immunology

Volumn 136, Issue 2, 2012, Pages 115-122

  Himmel, Megan E ^a   Yao, Yu ^a   Orban, Paul C ^a   Steiner, Theodore S ^a   Levings, Megan K ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Cellular therapy; Crohn's disease; Inflammatory bowel disease; Interleukin 10; Regulatory T cell

Indexed keywords

ADOPTIVE TRANSFER; CELL THERAPY; ENTERITIS; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; LYMPHOCYTE FUNCTION; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REGULATORY T LYMPHOCYTE THERAPY; REVIEW; THERAPY EFFECT; TREATMENT OUTCOME;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; INFLAMMATORY BOWEL DISEASES; INTESTINAL MUCOSA; MICE; T-LYMPHOCYTES, REGULATORY;

EID: 84860259163     PISSN: 00192805     EISSN: 13652567     Source Type: Journal    
DOI: 10.1111/j.1365-2567.2012.03572.x     Document Type: Review

References (98)

1. Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol 2008; 8:523-32.
2. + T regulatory cell-mediated suppression. Immunity 2009; 30:636-45.
3. Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T. Regulatory T cells: how do they suppress immune responses? Int Immunol 2009; 21:1105-11.
4. Rudensky AY. Regulatory T cells and Foxp3. Immunol Rev 2011; 241:260-8.
5. + regulatory T cells: more of the same or a division of labor? Immunity 2009; 30:626-35.
6. + regulatory T cells are not mirror images of each other. Trends Immunol 2008; 29:429-35.
7. 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 2006; 212:28-50.
8. + T cells induce or protect from chronic intestinal inflammation in C. B-17 SCID mice. Int Immunol 1993; 5:1461-71.
9. + T cells are important for the balance between protective and pathogenic cell-mediated immunity. J Exp Med 1994; 179:589-600.
10. + regulatory T cells. J Immunol 2003; 170:3939-43.
11. Gibbons DL, Spencer J. Mouse and human intestinal immunity: same ballpark, different players; different rules, same score. Mucosal Immunol 2011; 4:148-57.
12. Brunstein CG, Miller JS, Cao Q et al. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood 2010; 117:1061-70.
13. Di Ianni M, Falzetti F, Carotti A et al. Tregs prevent GvHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood 2011; 117:3921-8.
14. - T regulatory cells. Clin Immunol 2009; 133:22-6.
15. Edinger M, Hoffmann P. Regulatory T cells in stem cell transplantation: strategies and first clinical experiences. Curr Opin Immunol 2011; 23:679-84.
16. McMurchy AN, Bushell A, Levings MK, Wood KJ. Moving to tolerance: clinical application of T regulatory cells. Semin Immunol 2011; 23:304-13.
17. Izcue A, Powrie F. Special regulatory T-cell review: regulatory T cells and the intestinal tract - patrolling the frontier. Immunology 2008; 123:6-10.
18. Izcue A, Coombes JL, Powrie F. Regulatory lymphocytes and intestinal inflammation. Annu Rev Immunol 2009; 27:313-38.
19. Danese S, Fiocchi C. Ulcerative colitis. N Eng J Med 2011; 365:1713-25.
20. Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 2011; 474:298-306.
21. Hardenberg G, Steiner TS, Levings MK. Environmental influences on T regulatory cells in inflammatory bowel disease. Semin Immunol 2011; 23:130-8.
22. + T cells to proliferate and secrete interferon-γ. Am J Physiol Gastrointest Liver Physiol 2007; 292:G1630-40.
23. Brand S. Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease. Gut 2009; 58:1152-67.
24. + regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. J Clin Immunol 2010; 30:80-9.
25. Pene J, Chevalier S, Preisser L et al. Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunol 2008; 180:7423-30.
26. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007; 448:427-34.
27. Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 2003; 3:521-33.
28. Heller F, Florian P, Bojarski C et al. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 2005; 129:550-64.
29. Saleh M, Elson CO. Experimental inflammatory bowel disease: insights into the host-microbiota dialog. Immunity 2011; 34:293-302.
30. - precursor cells in the absence of interleukin 10. Nat Immunol 2007; 8:931-41.
31. Bacchetta R, Passerini L, Gambineri E et al. Defective regulatory and effector T cell functions in patients with FOXP3 mutations. J Clin Invest 2006; 116:1713-22.
32. McMurchy AN, Di Nunzio S, Roncarolo MG, Bacchetta R, Levings MK. Molecular regulation of cellular immunity by FOXP3. Adv Exp Med Biol 2009; 665:30-46.
33. + regulatory T cells. Nat Immunol 2003; 4:330-6.
34. + T cells in an interleukin-10-dependent manner. Immunity 2011; 34:554-65.
35. Rubtsov YP, Rasmussen JP, Chi EY et al. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 2008; 28:546-58.
36. Collison LW, Workman CJ, Kuo TT et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007; 450:566-9.
37. Konkel JE, Chen W. Balancing acts: the role of TGF-β in the mucosal immune system. Trends Mol Med 2011; 17:668-76.
38. high T cells in inflammatory bowel disease. Gastroenterology 2005; 128:1868-78.
39. + regulatory T cells in ulcerative colitis. Inflamm Bowel Dis 2007; 13:191-9.
40. high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity. Inflamm Bowel Dis 2006; 12:447-56.
41. Reikvam DH, Perminow G, Lyckander LG, Gran JM, Brandtzaeg P, Vatn M, Carlsen HS. Increase of regulatory T cells in ileal mucosa of untreated pediatric Crohn's disease patients. Scand J Gastroenterol 2011; 46:550-60.
42. Roncarolo MG, Gregori S. Is FOXP3 a bona fide marker for human regulatory T cells? Eur J Immunol 2008; 38:925-7.
43. + T cells. Curr Opin Immunol 2009; 21:281-5.
44. Veltkamp C, Anstaett M, Wahl K et al. Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by anti-TNFα treatment. Gut 2011; 60:1345-53.
45. + T regulatory cells in human autoimmunity: more than a numbers game. J Immunol 2011; 187:2061-6.
46. Fantini MC, Rizzo A, Fina D et al. Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression. Gastroenterology 2009; 136:1308-16.
47. Monteleone G, Kumberova A, Croft NM, McKenzie C, Steer HW, MacDonald TT. Blocking Smad7 restores TGF-β1 signaling in chronic inflammatory bowel disease. J Clin Invest 2001; 108:601-9.
48. + T cell receptors. Immunity 2004; 21:267-77.
49. + regulatory T cell expansion induced by antigen-driven interaction with intestinal epithelial cells independent of local dendritic cells. Gut 2009; 58:211-9.
50. + regulatory T cells in inflammatory bowel diseases. Inflamm Bowel Dis 2011; 17:160-70.
51. Hippen KL, Merkel SC, Schirm DK et al. Generation and large-scale expansion of human inducible regulatory T cells that suppress graft-versus-host disease. Am J Transplant 2011; 11:1148-57.
52. + regulatory T cells via a TGF-β and retinoic acid-dependent mechanism. J Exp Med 2007; 204:1757-64.
53. Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, Cheroutre H. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 2007; 317:256-60.
54. Sun CM, Hall JA, Blank RB, Bouladoux N, Oukka M, Mora JR, Belkaid Y. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 2007; 204:1775-85.
55. + dendritic cells: master regulators of tolerance? Trends Immunol 2011; 32:412-9.
56. Cassani B, Villablanca EJ, De Calisto J, Wang S, Mora JR. Vitamin A and immune regulation: role of retinoic acid in gut-associated dendritic cell education, immune protection and tolerance. Mol Aspects Med 2012; 33:63-76.
57. Kretschmer K, Heng TS, von Boehmer H. De novo production of antigen-specific suppressor cells in vivo. Nat Protoc 2006; 1:653-61.
58. Weiner HL, da Cunha AP, Quintana F, Wu H. Oral tolerance. Immunol Rev 2011; 241:241-59.
59. Murai M, Turovskaya O, Kim G, Madan R, Karp CL, Cheroutre H, Kronenberg M. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol 2009; 10:1178-84.
60. Li MC, He SH. IL-10 and its related cytokines for treatment of inflammatory bowel disease. World J Gastroenterol 2004; 10:620-5.
61. Braat H, Rottiers P, Hommes DW et al. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin Gastroenterol Hepatol 2006; 4:754-9.
62. Desreumaux P, Beaugerie L, Hebuterne X et al. First completed study with Type 1 regulatory (Tr1) lymphocytes in Crohn's disease. UEGW, Stockholm, SE, 2011.
63. Kendal AR, Waldmann H. Infectious tolerance: therapeutic potential. Curr Opin Immunol 2010; 22:560-5.
64. Zhou P, Borojevic R, Streutker C, Snider D, Liang H, Croitoru K. Expression of dual TCR on DO11.10 T cells allows for ovalbumin-induced oral tolerance to prevent T cell-mediated colitis directed against unrelated enteric bacterial antigens. J Immunol 2004; 172:1515-23.
65. + T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997; 389:737-42.
66. Duchmann R, May E, Heike M, Knolle P, Neurath M, Meyer zum Buschenfelde KH. T cell specificity and cross reactivity towards enterobacteria, bacteroides, bifidobacterium, and antigens from resident intestinal flora in humans. Gut 1999; 44:812-8.
67. + T cells reactive to enteric bacterial antigens in spontaneously colitic C3H/HeJBir mice: increased T helper cell type 1 response and ability to transfer disease. J Exp Med 1998; 187:855-64.
68. Lodes MJ, Cong Y, Elson CO, Mohamath R, Landers CJ, Targan SR, Fort M, Hershberg RM. Bacterial flagellin is a dominant antigen in Crohn disease. J Clin Invest 2004; 113:1296-306.
69. Rhee SH, Im E, Riegler M, Kokkotou E, O'Brien M, Pothoulakis C. Pathophysiological role of Toll-like receptor 5 engagement by bacterial flagellin in colonic inflammation. Proc Natl Acad Sci USA 2005; 102:13610-5.
70. Ivison SM, Himmel ME, Hardenberg G, Wark PA, Kifayet A, Levings MK, Steiner TS. TLR5 is not required for flagellin-mediated exacerbation of DSS colitis. Inflamm Bowel Dis 2010; 16:401-9.
71. Troncone R, Jabri B. Coeliac disease and gluten sensitivity. J Intern Med 2011; 269:582-90.
72. Di Sabatino A, Corazza GR. Coeliac disease. Lancet 2009; 373:1480-93.
73. Tiittanen M, Westerholm-Ormio M, Verkasalo M, Savilahti E, Vaarala O. Infiltration of forkhead box P3-expressing cells in small intestinal mucosa in coeliac disease but not in type 1 diabetes. Clin Exp Immunol 2008; 152:498-507.
74. Vorobjova T, Uibo O, Heilman K et al. Increased FOXP3 expression in small-bowel mucosa of children with coeliac disease and type I diabetes mellitus. Scand J Gastroenterol 2009; 44:422-30.
75. Brazowski E, Cohen S, Yaron A, Filip I, Eisenthal A. FOXP3 expression in duodenal mucosa in pediatric patients with celiac disease. Pathobiology 2010; 77:328-34.
76. Arranz E, Garrote JA. IL-15 modulates the effect of retinoic acid, promoting inflammation rather than oral tolerance to dietary antigens. Expert Rev Gastroenterol Hepatol 2011; 5:315-7.
77. Hmida NB, Ahmed MB, Moussa A et al. Impaired control of effector T cells by regulatory T cells: a clue to loss of oral tolerance and autoimmunity in celiac disease? Am J Gastroenterol 2011. DOI: 10.1038/ajg.2011.397. [Epub ahead of print].
78. Gianfrani C, Levings MK, Sartirana C et al. Gliadin-specific type 1 regulatory T cells from the intestinal mucosa of treated celiac patients inhibit pathogenic T cells. J Immunol 2006; 177:4178-86.
79. Raki M, Fallang LE, Brottveit M, Bergseng E, Quarsten H, Lundin KE, Sollid LM. Tetramer visualization of gut-homing gluten-specific T cells in the peripheral blood of celiac disease patients. Proc Natl Acad Sci USA 2007; 104:2831-6.
80. Fava F, Danese S. Intestinal microbiota in inflammatory bowel disease: friend of foe? World J Gastroenterol 2011; 17:557-66.
81. Lathrop SK, Bloom SM, Rao SM et al. Peripheral education of the immune system by colonic commensal microbiota. Nature 2011; 478:250-4.
82. Feng T, Wang L, Schoeb TR, Elson CO, Cong Y. Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis. J Exp Med 2010; 207:1321-32.
83. Geuking MB, Cahenzli J, Lawson MA, Ng DC, Slack E, Hapfelmeier S, McCoy KD, Macpherson AJ. Intestinal bacterial colonization induces mutualistic regulatory T cell responses. Immunity 2011; 34:794-806.
84. Atarashi K, Tanoue T, Shima T et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 2011; 331:337-41.
85. Round JL, Lee SM, Li J, Tran G, Jabri B, Chatila TA, Mazmanian SK. The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota. Science 2011; 332:974-7.
86. Forsythe P, Bienenstock J. Immunomodulation by commensal and probiotic bacteria. Immunol Invest 2010; 39:429-48.
87. H17 cell differentiation by antagonizing RORγt function. Nature 2008; 453:236-40.
88. Lee YK, Mazmanian SK. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 2010; 330:1768-73.
89. Hovhannisyan Z, Treatman J, Littman DR, Mayer L. Characterization of interleukin-17-producing regulatory T cells in inflamed intestinal mucosa from patients with inflammatory bowel diseases. Gastroenterology 2010; 140:957-65.
90. + T cells that inhibit colitis. Gastroenterology 2011; 140:2031-43.
91. + regulatory T cells. Nat Rev Immunol 2011; 11:119-30.
92. Newell KA, Asare A, Kirk AD et al. Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest 2010; 120:1836-47.
93. Sagoo P, Perucha E, Sawitzki B et al. Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans. J Clin Invest 2010; 120:1848-61.
94. Riley JL, June CH, Blazar BR. Human T regulatory cell therapy: take a billion or so and call me in the morning. Immunity 2009; 30:656-65.
95. + T reg cells. J Exp Med 2006; 203:1701-11.
96. + regulatory T cells. Proc Natl Acad Sci USA 2009; 106:13439-44.
97. high T cells gives rise to homogeneous regulatory T-cell lines upon in vitro expansion. Blood 2006; 108:4260-7.
98. + regulatory T cells. J Exp Med 2005; 201:737-46.