Dendritic cells and the promise of antigen-specific therapy in rheumatoid arthritis

Arthritis Research and Therapy

Volumn 15, Issue 1, 2013, Pages

  Thomas, Ranjeny ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIGEN; HLA DR ANTIGEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; T LYMPHOCYTE RECEPTOR;

AUTOIMMUNE DISEASE; CD4+ CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; DENDRITIC CELL; HUMAN; IMMUNOPATHOGENESIS; IMMUNOTHERAPY; INFLAMMATORY DISEASE; REGULATORY T LYMPHOCYTE; REVIEW; RHEUMATOID ARTHRITIS; VACCINATION; ANIMAL; AUTOIMMUNITY; IMMUNOLOGY; PROCEDURES;

ANIMALS; ARTHRITIS, RHEUMATOID; AUTOANTIGENS; AUTOIMMUNITY; DENDRITIC CELLS; HUMANS; IMMUNOTHERAPY;

EID: 84873525758     PISSN: 14786354     EISSN: 14786362     Source Type: Journal    
DOI: 10.1186/ar4130     Document Type: Review

References (114)

1. O'Dell JR, Haire CE, Erikson N, Drymalski W, Palmer W, Eckhoff PJ, Garwood V, Maloley P, Klassen LW, Wees S, Klein H, Moore GF. Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 1996, 334:1287-1291. 10.1056/NEJM199605163342002, 8609945.
2. Smolen JS, Landewé R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, Gorter S, Knevel R, Nam J, Schoels M, Aletaha D, Buch M, Gossec L, Huizinga T, Bijlsma JWJW, Burmester G, Combe B, Cutolo M, Gabay C, Gomez-Reino J, Kouloumas M, Kvien TK, Martin-Mola E, McInnes I, Pavelka K, van Riel P, Scholte M, Scott DL, Sokka T, Valesini G, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 2010, 69:964-975. 10.1136/ard.2009.126532, 2935329, 20444750.
3. Emery P, Dorner T. Optimising treatment in rheumatoid arthritis: a review of potential biological markers of response. Ann Rheum Dis 2011, 70:2063-2070. 10.1136/ard.2010.148015, 22039166.
4. Breedveld FC, Han C, Bala M, van der Heijde D, Baker D, Kavanaugh AF, Maini RN, Lipsky PE. Association between baseline radiographic damage and improvement in physical function after treatment of patients with rheumatoid arthritis. Ann Rheum Dis 2005, 64:52-55. 10.1136/ard.2003.017160, 1755174, 15286005.
5. Maradit-Kremers H, Nicola PJ, Crowson CS, Ballman KV, Gabriel SE. Cardiovascular death in rheumatoid arthritis: a population-based study. Arthritis Rheum 2005, 52:722-732. 10.1002/art.20878, 15751097.
6. Fautrel B, Verstappen SMM, Boonen A. Economic consequences and potential benefits. Best Pract Res Clin Rheumatol 2011, 25:607-624. 10.1016/j.berh.2011.10.001, 22137927.
7. Tsark EC, Wang W, Teng YC, Arkfeld D, Dodge GR, Kovats S. Differential MHC class II-mediated presentation of rheumatoid arthritis autoantigens by human dendritic cells and macrophages. J Immunol 2002, 169:6625-6633.
8. Blass S, Union A, Raymackers J, Schumann F, Ungethum U, Muller-Steinbach S, De Keyser F, Engel JM, Burmester GR. The stress protein BiP is overexpressed and is a major B and T cell target in rheumatoid arthritis. Arthritis Rheum 2001, 44:761-771. 10.1002/1529-0131(200104)44:4<761::AID-ANR132>3.0.CO;2-S, 11315915.
9. Yoo S-A, You S, Yoon H-J, Kim D-H, Kim H-S, Lee K, Ahn JH, Hwang D, Lee AS, Kim K-J, Park Y-J, Cho C-S, Kim W-U. A novel pathogenic role of the ER chaperone GRP78/BiP in rheumatoid arthritis. J Exp Med 2012, 209:871-886. 10.1084/jem.20111783, 3328363, 22430489.
10. Hasnain SZ, Lourie R, Das I, Chen ACH, McGuckin MA. The interplay between endoplasmic reticulum stress and inflammation. Immunol Cell Biol 2012, 90:260-270. 10.1038/icb.2011.112, 22249202.
11. Anzilotti C, Pratesi F, Tommasi C, Migliorini P. Peptidylarginine deiminase 4 and citrullination in health and disease. Autoimmun Rev 2010, 9:158-160. 10.1016/j.autrev.2009.06.002, 19540364.
12. Leeming DJ, Bay-Jensen AC, Vassiliadis E, Larsen MR, Henriksen K, Karsdal MA. Post-translational modifications of the extracellular matrix are key events in cancer progression: opportunities for biochemical marker development. Biomarkers 2011, 16:193-205. 10.3109/1354750X.2011.557440, 21506694.
13. Tanikawa C, Espinosa M, Suzuki A, Masuda K, Yamamoto K, Tsuchiya E, Ueda K, Daigo Y, Nakamura Y, Matsuda K. Regulation of histone modification and chromatin structure by the p53-PADI4 pathway. Nat Commun 2012, 3:676.
14. Vossenaar ER, Van Venrooij WJ. Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis. Arthritis Res Ther 2004, 6:107-111. 10.1186/ar1184, 416453, 15142259.
15. Masson-Bessiere C, Sebbag M, Girbal-Neuhauser E, Nogueira L, Vincent C, Senshu T, Serre G. The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the alpha- and beta-chains of fibrin. J Immunol 2001, 166:4177-4184.
16. Sokolove J, Bromberg R, Deane KD, Lahey LJ, Derber LA, Chandra PE, Edison JD, Gilliland WR, Tibshirani RJ, Norris JM, Holers VM, Robinson WH. Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS One 2012, 7:e35296. 10.1371/journal.pone.0035296, 3360701, 22662108.
17. Makrygiannakis D, Hermansson M, Ulfgren A-K, Nicholas AP, Zendman AJW, Eklund A, Grunewald J, Skold CM, Klareskog L, Catrina AI. Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells. Ann Rheum Dis 2008, 67:1488-1492. 10.1136/ard.2007.075192, 18413445.
18. Klareskog L, Stolt P, Lundberg K, Kallberg H, Bengtsson C, Grunewald J, Ronnelid J, Harris HE, Ulfgren AK, Rantapaa-Dahlqvist S, Eklund A, Padyukov L, Alfredsson L. A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 2006, 54:38-46. 10.1002/art.21575, 16385494.
19. Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis: an approach to understanding the molecular genetics of suseptibility to rheumatoid arthritis. Arthritis Rheum 1987, 30:1205-1213. 10.1002/art.1780301102, 2446635.
20. van der Helm-van Mil AHM, Verpoort KN, le Cessie S, Huizinga TWJ, de Vries RRP, Toes REM. The HLA-DRB1 shared epitope alleles differ in the interaction with smoking and predisposition to antibodies to cyclic citrullinated peptide. Arthritis Rheum 2007, 56:425-432. 10.1002/art.22373, 17265477.
21. Raychaudhuri S, Sandor C, Stahl EA, Freudenberg J, Lee H-S, Jia X, Alfredsson L, Padyukov L, Klareskog L, Worthington J, Siminovitch KA, Bae S-C, Plenge RM, Gregersen PK, de Bakker PIW. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Genet 2012, 44:291-296. 10.1038/ng.1076, 3288335, 22286218.
22. Thomas R, Turner M, Cope AP. High avidity autoreactive T cells with a low signalling capacity through the T-cell receptor: central to rheumatoid arthritis pathogenesis?. Arthritis Res Ther 2008, 10:210. 10.1186/ar2446, 2575618, 18710589.
23. Kim C-Y, Quarsten H, Bergseng E, Khosla C, Sollid LM. Structural basis for HLA-DQ2-mediated presentation of gluten epitopes in celiac disease. Proc Natl Acad Sci USA 2004, 101:4175-4179. 10.1073/pnas.0306885101, 384714, 15020763.
24. Mannering SI, Harrison LC, Williamson NA, Morris JS, Thearle DJ, Jensen KP, Kay TW, Rossjohn J, Falk BA, Nepom GT, Purcell AW. The insulin A-chain epitope recognized by human T cells is posttranslationally modified. J Exp Med 2005, 202:1191-1197. 10.1084/jem.20051251, 2213236, 16260488.
25. Hill JA, Bell DA, Brintnell W, Yue D, Wehrli B, Jevnikar AM, Lee DM, Hueber W, Robinson WH, Cairns E. Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice. J Exp Med 2008, 205:967-979. 10.1084/jem.20072051, 2292232, 18391064.
26. Hill JA, Southwood S, Sette A, Jevnikar AM, Bell DA, Cairns E. Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. J Immunol 2003, 171:538-541.
27. Law SC, Street S, Yu CH, Capini C, Ramnoruth S, Nel HJ, van Gorp E, Hyde C, Lau K, Pahau H, Purcell AW, Thomas R. T-cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis patients carrying HLADRB1 shared epitope alleles. Arthritis Res Ther 2012, 14:R118. 10.1186/ar3848, 3446499, 22594821.
28. von Delwig A, Locke J, Robinson JH, Ng WF. Response of Th17 cells to a citrullinated arthritogenic aggrecan peptide in patients with rheumatoid arthritis. Arthritis Rheum 2010, 62:143-149.
29. Snir O, Rieck M, Gebe JA, Yue BB, Rawlings CA, Nepom G, Malmström V, Buckner JH. Identification and functional characterization of T cells reactive to citrullinated vimentin in HLA-DRB1*0401-positive humanized mice and rheumatoid arthritis patients. Arthritis Rheum 2011, 63:2873-2883. 10.1002/art.30445, 3174345, 21567378.
30. Trentham DE, Dynesius-Trentham RA, Orav EJ, Combitchi D, Lorenzo C, Sewell KL, Hafler DA, Weiner HL. Effects of oral administration of type II collagen on rheumatoid arthritis. Science 1993, 261:1727-1730. 10.1126/science.8378772, 8378772.
31. Koffeman EC, Genovese M, Amox D, Keogh E, Santana E, Matteson EL, Kavanaugh A, Molitor JA, Schiff MH, Posever JO, Bathon JM, Kivitz AJ, Samodal R, Belardi F, Dennehey C, Van Den Broek T, van Wijk F, Zhang X, Zieseniss P, Le T, Prakken BA, Cutter GC, Albani S. Epitope-specific immunotherapy of rheumatoid arthritis: clinical responsiveness occurs with immune deviation and relies on the expression of a cluster of molecules associated with T cell tolerance in a double-blind, placebo-controlled, pilot phase II trial. Arthritis Rheum 2009, 60:3207-3216. 10.1002/art.24916, 19877047.
32. Kavanaugh A, Genovese M, Baughman J, Kivitz A, Bulpitt K, Olsen N, Weisman M, Matteson E, Furst D, van Vollenhoven R, Anderson J, Cohen S, Wei N, Meijerink J, Jacobs C, Mocci S. Allele and antigen-specific treatment of rheumatoid arthritis: a double blind, placebo controlled phase 1 trial. J Rheumatol 2003, 30:449-454.
33. Staines NA, Derry CJ, Marinova-Mutafchieva L, Ali N, Davies DH, Murphy JJ. Constraints on the efficacy of mucosal tolerance in treatment of human and animal arthritic diseases. Ann NY Acad Sci 2004, 1029:250-259. 10.1196/annals.1309.056, 15681763.
34. Ehrenstein MR, Evans JG, Singh A, Moore S, Warnes G, Isenberg DA, Mauri C. Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFα therapy. J Exp Med 2004, 200:277-285. 10.1084/jem.20040165, 2211983, 15280421.
35. Pettit AR, MacDonald KPA, O'Sullivan B, Thomas R. Differentiated dendritic cells expressing nuclear RelB are predominantly located in rheumatoid synovial tissue perivascular mononuclear cell aggregates. Arthritis Rheum 2000, 43:791-800. 10.1002/1529-0131(200004)43:4<791::AID-ANR9>3.0.CO;2-E, 10765923.
36. Thomas R, Quinn C. Functional differentiation of dendritic cells in rheumatoid arthritis: role of CD86 in the synovium. J Immunol 1996, 156:3074-3086.
37. Thomas R, Davis LS, Lipsky PE. Rheumatoid synovium is enriched in mature antigen-presenting dendritic cells. J Immunol 1994, 152:2613-2623.
38. Scher JU, Ubeda C, Equinda M, Khanin R, Buischi Y, Viale A, Lipuma L, Attur M, Pillinger MH, Weissmann G, Littman DR, Pamer EG, Bretz WA, Abramson SB. Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Arthritis Rheum 2012, 64:3083-3094. 10.1002/art.34539, 22576262.
39. Lutzky V, Hannawi S, Thomas R. Cells of the synovium in rheumatoid arthritis. Dendritic cells. Arthritis Res Ther 2007, 9:219. 10.1186/ar2200, 2206384, 17850683.
40. Kenna TJ, Thomas R, Steptoe R J. Steady-state dendritic cells expressing cognate antigen terminate memory CD8+ T-cell responses. Blood 2008, 111:2091-2100. 10.1182/blood-2007-07-103200, 18003887.
41. Zhang ZY, Lee CS, Lider O, Weiner HL. Suppression of adjuvant arthritis in Lewis rats by oral administration of type II collagen. J Immunol 1990, 145:2489-2493.
42. Thompson HS, Harper N, Bevan DJ, Staines NA. Suppression of collagen induced arthritis by oral administration of type II collagen: changes in immune and arthritic responses mediated by active peripheral suppression. Autoimmunity 1993, 16:189-199. 10.3109/08916939308993327, 8003614.
43. Min SY, Hwang SY, Park KS, Lee JS, Lee KE, Kim KW, Jung YO, Koh HJ, Do JH, Kim H, Kim HY. Induction of IL-10-producing CD4+CD25+ T cells in animal model of collagen-induced arthritis by oral administration of type II collagen. Arthritis Res Ther 2004, 6:R213-R219. 10.1186/ar1169, 416445, 15142267.
44. Billingham ME, Carney S, Butler R, Colston MJ. A mycobacterial 65-kD heat shock protein induces antigen-specific suppression of adjuvant arthritis, but is not itself arthritogenic. J Exp Med 1990, 171:339-344. 10.1084/jem.171.1.339, 2187658, 2104920.
45. Jorgensen C, Gedon E, Jaquet C, Sany J. Gastric administration of recombinant 65 kDa heat shock protein delays the severity of type II collagen induced arthritis in mice. J Rheumatol 1998, 25:763-767.
46. Sieper J, Kary S, Sorensen H, Alten R, Eggens U, Huge W, Hiepe F, Kuhne A, Listing J, Ulbrich N, Braun J, Zink A, Mitchison NA. Oral type II collagen treatment in early rheumatoid arthritis. A double-blind, placebo-controlled, randomized trial. Arthritis Rheum 1996, 39:41-51. 10.1002/art.1780390106, 8546737.
47. Barnett ML, Kremer JM, St Clair EW, Clegg DO, Furst D, Weisman M, Fletcher MJ, Chasan-Taber S, Finger E, Morales A, Le CH, Trentham DE. Treatment of rheumatoid arthritis with oral type II collagen. Results of a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 1998, 41:290-297. 10.1002/1529-0131(199802)41:2<290::AID-ART13>3.0.CO;2-R, 9485087.
48. McKown KM, Carbone LD, Kaplan SB, Aelion JA, Lohr KM, Cremer MA, Bustillo J, Gonzalez M, Kaeley G, Steere EL, Somes GW, Myers LK, Seyer JM, Kang AH, Postlethwaite AE. Lack of efficacy of oral bovine type II collagen added to existing therapy in rheumatoid arthritis. Arthritis Rheum 1999, 42:1204-1208. 10.1002/1529-0131(199906)42:6<1204::AID-ANR17>3.0.CO;2-U, 10366113.
49. Puga Yung GL, Le TD, Roord S, Prakken B, Albani S. Heat shock proteins (HSP) for immunotherapy of rheumatoid arthritis (RA). Inflamm Res 2003, 52:443-451. 10.1007/s00011-003-1204-6, 14652678.
50. Verstraeten A, Sileghem A, Dequeker J. OM-8980 and D-penicillamine in the treatment of rheumatoid arthritis. A 12-month double-blind randomized study. Scand J Rheumatol 1990, 19:422-431. 10.3109/03009749009097631, 2259898.
51. Prakken BJ, Samodal R, Le TD, Giannoni F, Yung GP, Scavulli J, Amox D, Roord S, de Kleer I, Bonnin D, Lanza P, Berry C, Massa M, Billetta R, Albani S. Epitopespecific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis. Proc Natl Acad Sci USA 2004, 101:4228-4233. 10.1073/pnas.0400061101, 384723, 15024101.
52. Koffeman EC, Genovese M, Amox D, Keogh E, Santana E, Matteson EL, Kavanaugh A, Molitor JA, Schiff MH, Posever JO, Bathon JM, Kivitz AJ, Samodal R, Belardi F, Dennehey C, Van Den Broek T, van Wijk F, Zhang X, Zieseniss P, Le T, Prakken BA, Cutter GC, Albani S. Epitope-specific immunotherapy of rheumatoid arthritis: clinical responsiveness occurs with immune deviation and relies on the expression of a cluster of molecules associated with T cell tolerance in a double-blind, placebo-controlled, pilot phase II trial. Arthritis Rheum 2009, 60:3207-3216. 10.1002/art.24916, 19877047.
53. Miles JJ, Douek DC, Price DA. Bias in the αβ T-cell repertoire: implications for disease pathogenesis and vaccination. Immunol Cell Biol 2011, 89:375-387. 10.1038/icb.2010.139, 21301479.
54. Williams WV, Fang Q, Demarco D, VonFeldt J, Zurier RB, Weiner DB. Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium. J Clin Investig 1992, 90:326-333. 10.1172/JCI115866, 443106, 1386608.
55. Jenkins RN, Nikaein A, Zimmermann A, Meek K, Lipsky PE. T cell receptor Vβ gene bias in rheumatoid arthritis. J Clin Investig 1993, 92:2688-2701. 10.1172/JCI116886, 288467, 8254025.
56. Li Y, Sun GR, Tumang JR, Crow MK, Friedman SM. CDR3 sequence motifs shared by oligoclonal rheumatoid arthritis synovial T cells. Evidence for an antigen-driven response. J Clin Investig 1994, 94:2525-2531. 10.1172/JCI117624, 330088, 7989613.
57. Sun W, Nie H, Li N, Zang YCQ, Zhang D, Feng G, Ni L, Xu R, Prasad S, Robinson RR, Ho W, Sercarz E, Zhang JZ. Skewed T-cell receptor BV14 and BV16 expression and shared CDR3 sequence and common sequence motifs in synovial T cells of rheumatoid arthritis. Genes Immun 2005, 6:248-261. 10.1038/sj.gene.6364166, 15674392.
58. Klarenbeek PL, de Hair MJH, Doorenspleet ME, van Schaik BDC, Esveldt REE, van de Sande MGH, Cantaert T, Gerlag DM, Baeten D, van Kampen AHC, Baas F, Tak PP, de Vries N. Inflamed target tissue provides a specific niche for highly expanded T-cell clones in early human autoimmune disease. Ann Rheum Dis 2012, 71:1088-1093. 10.1136/annrheumdis-2011-200612, 22294635.
59. Cohen IR. Lines of T lymphocytes induce or vaccinate against autoimmune arthritis. Science 1983, 219:56-58. 10.1126/science.6336851, 6336851.
60. Zang YCQ, Hong J, Rivera VM, Killian J, Zhang JZ. Preferential recognition of TCR hypervariable regions by human anti-idiotypic T cells induced by T cell vaccination. J Immunol 2000, 164:4011-4017.
61. Correale J, Farez M, Gilmore W. Vaccines for multiple sclerosis: progress to date. CNS Drugs 2008, 22:175-198. 10.2165/00023210-200822030-00001, 18278975.
62. Moreland LW, Morgan EE, Adamson TC, Fronek Z, Calabrese LH, Cash JM, Markenson JA, Matsumoto AK, Bathon J, Matteson EL, Uramoto KM, Weyand CM, Koopman WJ, Heck LW, Strand V, Diveley JP, Carlo DJ, Nardo CJ, Richieri SP, Brostoff SW. T cell receptor peptide vaccination in rheumatoid arthritis: a placebo-controlled trial using a combination of Vβ3, Vβ14, and Vβ17 peptides. Arthritis Rheum 1998, 41:1919-1929. 10.1002/1529-0131(199811)41:11<1919::AID-ART5>3.0.CO;2-1, 9811045.
63. Nishizuka Y, Sakakura T. Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 1969, 166:753-755. 10.1126/science.166.3906.753, 5823314.
64. Kojima A, Tanaka-Kojima Y, Sakakura T, Nishizuka Y. Prevention of postthymectomy autoimmune thyroiditis in mice. Lab Invest 1976, 34:601-605.
65. 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.
66. Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, Kuniyasu Y, Nomura T, Toda M, Takahashi T. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev 2001, 182:18-32. 10.1034/j.1600-065X.2001.1820102.x, 11722621.
67. Sakaguchi S, Takahashi T, Yamazaki S, Kuniyasu Y, Itoh M, Sakaguchi N, Shimizu J. Immunologic self tolerance maintained by T-cell-mediated control of self-reactive T cells: implications for autoimmunity and tumor immunity. Microbes Infect 2001, 3:911-918. 10.1016/S1286-4579(01)01452-6, 11564439.
68. McHugh RS, Shevach EM, Thornton AM. Control of organ-specific autoimmunity by immunoregulatory CD4+CD25+ T cells. Microbes Infect 2001, 3:919-927. 10.1016/S1286-4579(01)01453-8, 11564440.
69. Singh B, Read S, Asseman C, Malmstrom V, Mottet C, Stephens LA, Stepankova R, Tlaskalova H, Powrie F. Control of intestinal inflammation by regulatory T cells. Immunol Rev 2001, 182:190-200. 10.1034/j.1600-065X.2001.1820115.x, 11722634.
70. Fehervari Z, Yamaguchi T, Sakaguchi S. The dichotomous role of IL-2: tolerance versus immunity. Trends Immunol 2006, 27:109-111. 10.1016/j.it.2006.01.005, 16459146.
71. Charbonnier L-M, Han WGH, Quentin J, Huizinga TWJ, Zwerina J, Toes REM, Jorgensen C, Louis-Plence P. Adoptive transfer of IL-10-secreting CD4+CD49b+ regulatory T cells suppresses ongoing arthritis. J Autoimmun 2010, 34:390-399. 10.1016/j.jaut.2009.10.003, 19880290.
72. Morgan ME, Flierman R, van Duivenvoorde LM, Witteveen HJ, van Ewijk W, van Laar JM, de vries RRP, Toes REM. Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells. Arthritis Rheum 2005, 52:2212-2221. 10.1002/art.21195, 15986351.
73. Tarbell KV, Petit L, Zuo X, Toy P, Luo X, Mqadmi A, Yang H, Suthanthiran M, Mojsov S, Steinman RM. Dendritic cell-expanded, islet-specific CD4+CD25+CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. J Exp Med 2007, 204:191-201. 10.1084/jem.20061631, 2118426, 17210729.
74. Putnam AL, Brusko TM, Lee MR, Liu W, Szot GL, Ghosh T, Atkinson MA, Bluestone JA. Expansion of human regulatory T-cells from patients with type 1 diabetes. Diabetes 2009, 58:652-662. 2646064, 19074986.
75. Groux H, O'Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, Roncarolo MG. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997, 389:737-742. 10.1038/39614, 9338786.
76. Levings MK, Gregori S, Tresoldi E, Cazzaniga S, Bonini C, Roncarolo MG. Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood 2005, 105:1162-1169.
77. Bacchetta R, de Waal Malefijt R, Yssel H, Abrams J, de Vries JE, Spits H, Roncarolo MG. 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.
78. Roncarolo M-G, Gregori S, Lucarelli B, Ciceri F, Bacchetta R. Clinical tolerance in allogeneic hematopoietic stem cell transplantation. Immunol Rev 2011, 241:145-163. 10.1111/j.1600-065X.2011.01010.x, 21488896.
79. Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, Hall J, Sun CM, 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. 10.1084/jem.20070590, 2118683, 17620361.
80. Benson MJ, Pino-Lagos K, Rosemblatt M, Noelle RJ. All-trans retinoic acid mediates enhanced Treg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J Exp Med 2007, 204:1765-1774. 10.1084/jem.20070719, 2118687, 17620363.
81. Annacker O, Coombes JL, Malmstrom V, Uhlig HH, Bourne T, Johansson-Lindbom B, Agace WW, Parker CM, Powrie F. Essential role for CD103 in the T cell-mediated regulation of experimental colitis. J Exp Med 2005, 202:1051-1061. 10.1084/jem.20040662, 2213206, 16216886.
82. 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, 204:1775-1785. 10.1084/jem.20070602, 2118682, 17620362.
83. Kang SG, Lim HW, Andrisani OM, Broxmeyer HE, Kim CH. Vitam in A metabolites induce gut-homing FoxP3+ regulatory T cells. J Immunol 2007, 179:3724-3733.
84. Schambach F, Schupp M, Lazar MA, Reiner SL. Activation of retinoic acid receptor-alpha favours regulatory T cell induction at the expense of IL-17secreting T helper cell differentiation. Eur J Immunol 2007, 37:2396-2399. 10.1002/eji.200737621, 17694576.
85. 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, 317:256-260. 10.1126/science.1145697, 17569825.
86. Neumann M, Fries H, Scheicher C, Keikavoussi P, Kolb-Maurer A, Brocker E, Serfling E, Kampgen E. Differential expression of Rel/NF-kappaB and octamer factors is a hallmark of the generation and maturation of dendritic cells. Blood 2000, 95:277-285.
87. Pettit AR, Quinn C, MacDonald KP, Cavanagh LL, Thomas G, Townsend W, Handel M, Thomas R. Nuclear localization of RelB is associated with effective antigen-presenting cell function. J Immunol 1997, 159:3681-3691.
88. Burkly L, Hession C, Ogata L, Reilly C, Marconi LA, Olson D, Tizard R, Cate R, Lo D. Expression of relB is required for the development of thymic medulla and dendritic cells. Nature 1995, 373:531-536. 10.1038/373531a0, 7845467.
89. Weih F, Carrasco D, Durham SK, Barton DS, Rizzo CA, Ryseck RP, Lira SA, Bravo R. Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family. Cell 1995, 80:331-340. 10.1016/0092-8674(95)90416-6, 7834753.
90. Wu L, D'Amico A, Winkel KD, Suter M, Lo D, Shortman K. RelB is essential for the development of myeloid-related CD8α- dendritic cells but not of lymphoid-related CD8α+ dendritic cells. Immunity 1998, 9:839-847. 10.1016/S1074-7613(00)80649-4, 9881974.
91. O'Sullivan BJ, MacDonald KP, Pettit AR, Thomas R. RelB nuclear translocation regulates B cell MHC molecule, CD40 expression, and antigen-presenting cell function. Proc Natl Acad Sci USA 2000, 97:11421-11426. 10.1073/pnas.97.21.11421, 17215, 11027342.
92. Pai S, O'Sullivan BJ, Cooper L, Thomas R, Khanna R. RelB nuclear translocation mediated by C-terminal activator regions of Epstein-Barr virus-encoded latent membrane protein 1 and its effect on antigen-presenting function in B cells. J Virol 2002, 76:1914-1921. 10.1128/JVI.76.4.1914-1921.2002, 135895, 11799186.
93. Cobbold S, Waldmann H. Infectious tolerance. Curr Opin Immunol 1998, 10:518-524. 10.1016/S0952-7915(98)80217-3, 9794831.
94. Martin E, O'Sullivan BJ, Low P, Thomas R. Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10. Immunity 2003, 18:155-167. 10.1016/S1074-7613(02)00503-4, 12530984.
95. Li M, Zhang X, Zheng X, Lian D, Zhang ZX, Ge W, Yang J, Vladau C, Suzuki M, Chen D, Zhong R, Garcia B, Jevnikar AM, Min WP. Immune modulation and tolerance induction by RelB-silenced dendritic cells through RNA interference. J Immunol 2007, 178:5480-5487.
96. Thompson AG, O'Sullivan BJ, Beamish H, Thomas R. T cells signaled by NF-κB- dendritic cells are sensitized not anergic to subsequent activation. J Immunol 2004, 173:1671-1680.
97. Martin E, Capini C, Duggan E, Lutzky VP, Stumbles P, Pettit AR, O'Sullivan B, Thomas R. Antigen-specific suppression of established arthritis in mice by dendritic cells deficient in NF-κB. Arthritis Rheum 2007, 56:2255-2266. 10.1002/art.22655, 17599748.
98. Thomas R, Street S, Ramnoruth N, Pahau H, Law SC, Brunck M, Hyde C, O'Sullivan BJ, Capini C, Tran A, Ng J, Paul S. Feasibility, safety and clinical effects of a single intradermal administration of autologous tolerising dendritic cells exposed to citrullinated peptides in patients with rheumatoid arthritis [abstract]. Arthritis Rheum 2011, 63.
99. Yoshimura S, Bonderson J, Brennan FM, Foxwell BM, Feldmann M. Role of NF-κB in antigen presentation and development of regulatory T cells elucidated by treatment of dendritic cells with protease inhibitor PSI. Eur J Immunol 2001, 31:1883-1893. 10.1002/1521-4141(200106)31:6<1883::AID-IMMU1883>3.0.CO;2-V, 11433385.
100. Geisel J, Kahl F, Muller M, Wagner H, Kirschning CJ, Autenrieth IB, Frick JS. IL-6 and maturation govern TLR2 and TLR4 induced TLR agonist tolerance and cross-tolerance in dendritic cells. J Immunol 2007, 179:5811-5818.
101. Turnquist HR, Raimondi G, Zahorchak AF, Fischer RT, Wang Z, Thomson AW. Rapamycin-conditioned dendritic cells are poor stimulators of allogeneic CD4+ T cells, but enrich for antigen-specific Foxp3+ T regulatory cells and promote organ transplant tolerance. J Immunol 2007, 178:7018-7031.
102. Dong X, Lutz W, Schroeder TM, Bachman LA, Westendorf JJ, Kumar R, Griffin MD. Regulation of relB in dendritic cells by means of modulated association of vitamin D receptor and histone deacetylase 3 with the promoter. Proc Natl Acad Sci USA 2005, 102:16007-16012. 10.1073/pnas.0506516102, 1257750, 16239345.
103. Stoop JN, Harry RA, von Delwig A, Isaacs JD, Robinson JH, Hilkens CM. Therapeutic effect of tolerogenic dendritic cells in established collagen-induced arthritis is associated with a reduction in Th17 responses. Arthritis Rheum 2010, 62:3656-3665. 10.1002/art.27756, 20862679.
104. Harry RA, Anderson AE, Isaacs JD, Hilkens CM. Generation and characterisation of therapeutic tolerogenic dendritic cells for rheumatoid arthritis. Ann Rheum Dis 2010, 69:2042-2050. 10.1136/ard.2009.126383, 3002758, 20551157.
105. Giannoukakis N, Phillips B, Finegold D, Harnaha J, Trucco M. Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. Diabetes Care 2011, 34:2026-2032. 10.2337/dc11-0472, 3161299, 21680720.
106. Capini C, Jaturanpinyo M, Chang HI, Mutalik S, McNally A, Street S, Steptoe R, O'Sullivan B, Davies N, Thomas R. Antigen-specific suppression of inflammatory arthritis using liposomes. J Immunol 2009, 182:3556-3565. 10.4049/jimmunol.0802972, 19265134.
107. Pack CD, Cestra AE, Min B, Legge KL, Li L, Caprio-Young JC, Bell JJ, Gregg RK, Zaghouani H. Neonatal exposure to antigen primes the immune system to develop responses in various lymphoid organs and promotes bystander regulation of diverse T cell specificities. J Immunol 2001, 167:4187-4195.
108. Vanderlugt CL, Miller SD. Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol 2002, 2:85-95. 10.1038/nri724, 11910899.
109. Vollers SS, Stern LJ. Class II major histocompatibility complex tetramer staining: progress, problems, and prospects. Immunology 2008, 123:305-313. 10.1111/j.1365-2567.2007.02801.x, 2433336, 18251991.
110. Newell EW, Klein LO, Yu W, Davis MM. Simultaneous detection of many T-cell specificities using combinatorial tetramer staining. Nat Methods 2009, 6:497-499. 10.1038/nmeth.1344, 2731062, 19543286.
111. van de Stadt LA, de Koning MHMT, van de Stadt RJ, Wolbink G, Dijkmans BAC, Hamann D, van Schaardenburg D. Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis. Arthritis Rheum 2011, 63:3226-3233. 10.1002/art.30537, 21792832.
112. Deane KD, O'Donnell CI, Hueber W, Majka DS, Lazar AA, Derber LA, Gilliland WR, Edison JD, Norris JM, Robinson WH, Holers VM. The number of elevated cytokines and chemokines in preclinical seropositive rheumatoid arthritis predicts time to diagnosis in an age-dependent manner. Arthritis Rheum 2010, 62:3161-3172. 10.1002/art.27638, 2980824, 20597112.
113. Berglin E, Padyukov L, Sundin U, Hallmans G, Stenlund H, Van Venrooij WJ, Klareskog L, Dahlqvist SR. A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis. Arthritis Res Ther 2004, 6:R303-R308. 10.1186/ar1187, 464874, 15225365.
114. van Gaalen FA, van Aken J, Huizinga TW, Schreuder GM, Breedveld FC, Zanelli E, van Venrooij WJ, Verweij CL, Toes RE, de Vries RR. Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides (CCPs) influences the severity of rheumatoid arthritis. Arthritis Rheum 2004, 50:2113-2121. 10.1002/art.20316, 15248208.