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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 6/2008

01-12-2008 | Review

Regulatory T cells in systemic lupus erythematosus: past, present and future

Author: David A Horwitz

Published in: Arthritis Research & Therapy | Issue 6/2008

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Abstract

Regulatory/suppressor T cells (Tregs) maintain immunologic homeo-stasis and prevent autoimmunity. In this article, past studies and recent studies of Tregs in mouse models for lupus and of human systemic lupus erythematosus are reviewed concentrating on CD4+CD25+Foxp3+ Tregs. These cells consist of thymus-derived, natural Tregs and peripherally induced Tregs that are similar phenotypically and functionally. These Tregs are decreased in young lupus-prone mice, but are present in normal numbers in mice with established disease. In humans, most workers report CD4+Tregs are decreased in subjects with active systemic lupus erythematosus, but the cells increase with treatment and clinical improvement. The role of immunogenic and tolerogenic dendritic cells in controlling Tregs is discussed, along with new strategies to normalize Treg function in systemic lupus erythematosus.
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Literature
1.
Teague PO, Friou GJ: Antinuclear antibodies in mice. II. Transmission with spleen cells; inhibition or prevention with thymus or spleen cells. Immunology. 1969, 17: 665-675.PubMedCentralPubMed
2.
Krakauer RS, Strober W, Rippeon DL, Waldmann TA: Prevention of autoimmunity in experimental lupus erythematosus by soluble immune response suppressor. Science. 1977, 196: 56-59. 10.1126/science.300174.CrossRefPubMed
3.
Horwitz DA, Gray JD, editors: The interaction of T cells with cells of the innate immune system and B cells in the pathogenesis of SLE. Dubois' lupus erythematosus. 2007, New York: Lippincott Williams & Wilkins, 133-160. 7
4.
Asano M, Toda M, Sakaguchi N, Sakaguchi S: Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J Exp Med. 1996, 184: 387-396. 10.1084/jem.184.2.387.CrossRefPubMed
5.
Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z, Shimizu J, Takahashi T, Nomura T: Foxp3+ CD25+CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev. 2006, 212: 8-27. 10.1111/j.0105-2896.2006.00427.x.CrossRefPubMed
6.
Lan RY, Ansari AA, Lian ZX, Gershwin ME: Regulatory T cells: development, function and role in autoimmunity. Autoimmun Rev. 2005, 4: 351-363. 10.1016/j.autrev.2005.01.007.CrossRefPubMed
7.
Kim JM, Rasmussen JP, Rudensky AY: Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol. 2007, 8: 191-197. 10.1038/ni1428.CrossRefPubMed
8.
Wildin RS, Ramsdell F, Peake J, Faravelli F, Casanova JL, Buist N, Levy-Lahad E, Mazzella M, Goulet O, Perroni L, Bricarelli FD, Byrne G, McEuen M, Proll S, Appleby M, Brunkow ME: X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001, 27: 18-20. 10.1038/83707.CrossRefPubMed
9.
Godo M, Sessler T, Hamar P: Role of invariant natural killer T (iNKT) cells in systemic lupus erythematosus. Curr Med Chem. 2008, 15: 1778-1787. 10.2174/092986708785132988.CrossRefPubMed
10.
Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA: CD4+CD25high regulatory cells in human peripheral blood. J Immunol. 2001, 167: 1245-1253.CrossRefPubMed
11.
Gavin MA, Torgerson TR, Houston E, DeRoos P, Ho WY, Stray-Pedersen A, Ocheltree EL, Greenberg PD, Ochs HD, Rudensky AY: Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc Natl Acad Sci USA. 2006, 103: 6659-6664. 10.1073/pnas.0509484103.PubMedCentralCrossRefPubMed
12.
Pillai V, Ortega SB, Wang CK, Karandikar NJ: Transient regulatory T-cells: a state attained by all activated human T-cells. Clin Immunol. 2007, 123: 18-29. 10.1016/j.clim.2006.10.014.PubMedCentralCrossRefPubMed
13.
Horwitz DA, Zheng SG, Wang J, Gray JD: Critical role of IL-2 and TGF-β in generation, function and stabilization of Foxp3(+)CD4(+) Treg. Eur J Immunol. 2008, 38: 912-915. 10.1002/eji.200738109.CrossRefPubMed
14.
Bluestone JA, Abbas AK: Natural versus adaptive regulatory T cells. Nat Rev Immunol. 2003, 3: 253-257. 10.1038/nri1032.CrossRefPubMed
15.
Horwitz DA, Zheng SG, Gray JD: Natural and TGF-β-induced Foxp3(+)CD4(+)CD25(+) regulatory T cells are not mirror images of each other. Trends Immunol. 2008, 29: 429-435. 10.1016/j.it.2008.06.005.CrossRefPubMed
16.
Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY: A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol. 2005, 6: 1142-1151. 10.1038/ni1263.CrossRefPubMed
17.
Marie JC, Letterio JJ, Gavin M, Rudensky AY: TGF-β1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J Exp Med. 2005, 201: 1061-1067. 10.1084/jem.20042276.PubMedCentralCrossRefPubMed
18.
Bagavant H, Tung KS: Failure of CD25+ T cells from lupus-prone mice to suppress lupus glomerulonephritis and sialoadenitis. J Immunol. 2005, 175: 944-950.CrossRefPubMed
19.
Hayashi T, Hasegawa K, Adachi C: Elimination of CD4(+)CD25(+) T cell accelerates the development of glomerulonephritis during the preactive phase in autoimmune-prone female NZB × NZW F mice. Int J Exp Pathol. 2005, 86: 289-296. 10.1111/j.0959-9673.2005.00438.x.PubMedCentralCrossRefPubMed
20.
Scalapino KJ, Tang Q, Bluestone JA, Bonyhadi ML, Daikh DI: Suppression of disease in New Zealand Black/New Zealand White lupus-prone mice by adoptive transfer of ex vivo expanded regulatory T cells. J Immunol. 2006, 177: 1451-1459.CrossRefPubMed
21.
Hsu WT, Suen JL, Chiang BL: The role of CD4CD25 T cells in autoantibody production in murine lupus. Clin Exp Immunol. 2006, 145: 513-519. 10.1111/j.1365-2249.2006.03173.x.PubMedCentralCrossRefPubMed
22.
Liu MF, Wang CR, Fung LL, Wu CR: Decreased CD4+CD25+ T cells in peripheral blood of patients with systemic lupus erythematosus. Scand J Immunol. 2004, 59: 198-202. 10.1111/j.0300-9475.2004.01370.x.CrossRefPubMed
23.
Theofilopoulos AN, Shawler DL, Eisenberg RA, Dixon FJ: Splenic immunoglobulin-secreting cells and their regulation in autoimmune mice. J Exp Med. 1980, 151: 446-466. 10.1084/jem.151.2.446.CrossRefPubMed
24.
Zielinski CE, Jacob SN, Bouzahzah F, Ehrlich BE, Craft J: Naive CD4+ T cells from lupus-prone Fas-intact MRL mice display TCR-mediated hyperproliferation due to intrinsic threshold defects in activation. J Immunol. 2005, 174: 5100-5109.CrossRefPubMed
25.
Monk CR, Spachidou M, Rovis F, Leung E, Botto M, Lechler RI, Garden OA: MRL/Mp CD4+, CD25- T cells show reduced sensitivity to suppression by CD4+, CD25+regulatory T cells in vitro: a novel defect of T cell regulation in systemic lupus erythe-matosus. Arthritis Rheum. 2005, 52: 1180-1184. 10.1002/art.20976.CrossRefPubMed
26.
Pasare C, Medzhitov R: Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science. 2003, 299: 1033-1036. 10.1126/science.1078231.CrossRefPubMed
27.
Zheng SG, Wang JH, Koss MN, Quismorio F, Gray JD, Horwitz DA: CD4+ and CD8+ regulatory T cells generated ex vivo with IL-2 and TGF-β suppress a stimulatory graft-versus-host disease with a lupus-like syndrome. J Immunol. 2004, 172: 1531-1539.CrossRefPubMed
28.
Godebu E, Summers-Torres D, Lin MM, Baaten BJ, Bradley LM: Polyclonal adaptive regulatory CD4 cells that can reverse type I diabetes become oligoclonal long-term protective memory cells. J Immunol. 2008, 181: 1798-1805.PubMedCentralCrossRefPubMed
29.
Xu L, Kitani A, Fuss I, Strober W: Cutting edge: regulatory T cells induce CD4+CD25-Foxp3- T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-β. J Immunol. 2007, 178: 6725-6729.CrossRefPubMed
30.
Wong CK, Lit LC, Tam LS, Li EK, Wong PT, Lam CW: Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: Implications for Th17-mediated inflammation in auto-immunity. Clin Immunol. 2008, 127: 385-393. 10.1016/j.clim.2008.01.019.CrossRefPubMed
31.
Zheng SG, Wang J, Horwitz DA: Foxp3+ CD4+CD25+ regulatory T cells induced by IL-2 and TGF-β are resistant to Th17 conversion by IL-6. J Immunol. 2008, 180: 7112-7116.CrossRefPubMed
32.
Kang HK, Liu M, Datta SK: Low-dose peptide tolerance therapy of lupus generates plasmacytoid dendritic cells that cause expansion of autoantigen-specific regulatory T cells and contraction of inflammatory Th17 cells. J Immunol. 2007, 178: 7849-7858.CrossRefPubMed
33.
Wu HY, Staines NA: A deficiency of CD4+CD25+T cells permits the development of spontaneous lupus-like disease in mice, and can be reversed by induction of mucosal tolerance to histone peptide autoantigen. Lupus. 2004, 13: 192-200. 10.1191/0961203303lu1002oa.CrossRefPubMed
34.
Eilat E, Zinger H, Nyska A, Mozes E: Prevention of systemic lupus erythematosus-like disease in (NZBxNZW)F1 mice by treating with CDR1- and CDR3-based peptides of a pathogenic autoantibody. J Clin Immunol. 2000, 20: 268-278. 10.1023/A:1006663519132.CrossRefPubMed
35.
Hahn BH, Singh RP, La Cava A, Ebling FM: Tolerogenic treatment of lupus mice with consensus peptide induces Foxp3-expressing, apoptosis-resistant, TGFβ-secreting CD8+ T cell suppressors. J Immunol. 2005, 175: 7728-7737.CrossRefPubMed
36.
Riemekasten G, Langnickel D, Enghard P, Undeutsch R, Humrich J, Ebling FM, Hocher B, Humaljoki T, Neumayer H, Burmester GR, Hahn BH, Radbruch A, Hiepe F: Intravenous injection of a D1 protein of the Smith proteins postpones murine lupus and induces type 1 regulatory T cells. J Immunol. 2004, 173: 5835-5842.CrossRefPubMed
37.
Kaliyaperumal A, Michaels MA, Datta SK: Naturally processed chromatin peptides reveal a major autoepitope that primes pathogenic T and B cells of lupus. J Immunol. 2002, 168: 2530-2537.CrossRefPubMed
38.
Singh RP, La Cava A, Hahn BH: pConsensus peptide induces tolerogenic CD8+ T cells in lupus-prone (NZB × NZW)F1 mice by differentially regulating Foxp3 and PD1 molecules. J Immunol. 2008, 180: 2069-2080.CrossRefPubMed
39.
Singh RP, La Cava A, Wong M, Ebling F, Hahn BH: CD8+T cell-mediated suppression of autoimmunity in a murine lupus model of peptide-induced immune tolerance depends on Foxp3 expression. J Immunol. 2007, 178: 7649-7657.CrossRefPubMed
40.
Banchereau J, Pascual V: Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity. 2006, 25: 383-392. 10.1016/j.immuni.2006.08.010.CrossRefPubMed
41.
Filaci G, Bacilieri S, Fravega M, Monetti M, Contini P, Ghio M, Setti M, Puppo F, Indiveri F: Impairment of CD8+ T suppressor cell function in patients with active systemic lupus erythematosus. J Immunol. 2001, 166: 6452-6457.CrossRefPubMed
42.
Crispin JC, Martinez A, Alcocer-Varela J: Quantification of regulatory T cells in patients with systemic lupus erythematosus. J Autoimmun. 2003, 21: 273-276. 10.1016/S0896-8411(03)00121-5.CrossRefPubMed
43.
Fathy A, Mohamed RW, Tawfik GA, Omar AS: Diminished CD4+CD25+ T-lymphocytes in peripheral blood of patients with systemic lupus erythematosus. Egypt J Immunol. 2005, 12: 25-31.PubMed
44.
Lee JH, Wang LC, Lin YT, Yang YH, Lin DT, Chiang BL: Inverse correlation between CD4+ regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus. Immunology. 2006, 117: 280-286. 10.1111/j.1365-2567.2005.02306.x.PubMedCentralCrossRefPubMed
45.
Yang XY, Lu XY, Xu DH, Lu QH, Wang QH, Wu HX: Clinical significance of CD4+CD25+ T cells in peripheral blood of patients in systemic lupus erythematosus. Zhonghua Nei Ke Za Zhi. 2005, 44: 570-572.PubMed
46.
Barath S, Aleksza M, Tarr T, Sipka S, Szegedi G, Kiss E: Measurement of natural (CD4+CD25high) and inducible (CD4+IL-10+) regulatory T cells in patients with systemic lupus erythematosus. Lupus. 2007, 16: 489-496. 10.1177/0961203307080226.CrossRefPubMed
47.
Bonelli M, von Dalwigk K, Savitskaya A, Smolen JS, Scheinecker C: Foxp3 expression in CD4+ T cells of patients with systemic lupus erythematosus: a comparative phenotypic analysis. Ann Rheum Dis. 2008, 67: 664-671. 10.1136/ard.2007.074690.CrossRefPubMed
48.
Lyssuk EY, Torgashina AV, Soloviev SK, Nassonov EL, Bykovskaia SN: Reduced number and function of CD4+CD25highFoxP3+ regulatory T cells in patients with systemic lupus erythematosus. Adv Exp Med Biol. 2007, 601: 113-119.CrossRefPubMed
49.
Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S, Nochy D, Debre P, Piette JC, Gorochov G: Global natural regulatory T cell depletion in active systemic lupus erythematosus. J Immunol. 2005, 175: 8392-8400.CrossRefPubMed
50.
Valencia X, Yarboro C, Illei G, Lipsky PE: Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J Immunol. 2007, 178: 2579-2588.CrossRefPubMed
51.
Lee HY, Hong YK, Yun HJ, Kim YM, Kim JR, Yoo WH: Altered frequency and migration capacity of CD4+CD25+regulatory T cells in systemic lupus erythematosus. Rheumatology (Oxford). 2008, 47: 789-794. 10.1093/rheumatology/ken108.CrossRef
52.
Mellor-Pita S, Citores MJ, Castejon R, Tutor-Ureta P, Yebra-Bango M, Andreu JL, Vargas JA: Decrease of regulatory T cells in patients with systemic lupus erythematosus. Ann Rheum Dis. 2006, 65: 553-554. 10.1136/ard.2005.044974.PubMedCentralCrossRefPubMed
53.
Suarez A, Lopez P, Gomez J, Gutierrez C: Enrichment of CD4+CD25high T cell population in patients with systemic lupus erythematosus treated with glucocorticoids. Ann Rheum Dis. 2006, 65: 1512-1517. 10.1136/ard.2005.049924.PubMedCentralCrossRefPubMed
54.
Barath S, Soltesz P, Kiss E, Aleksza M, Zeher M, Szegedi G, Sipka S: The severity of systemic lupus erythematosus negatively correlates with the increasing number of CD4+CD25(high)FoxP3+ regulatory T cells during repeated plasmapheresis treatments of patients. Autoimmunity. 2007, 40: 521-528. 10.1080/08916930701610028.CrossRefPubMed
55.
Sfikakis PP, Souliotis VL, Fragiadaki KG, Moutsopoulos HM, Boletis JN, Theofilopoulos AN: Increased expression of the FoxP3 functional marker of regulatory T cells following B cell depletion with rituximab in patients with lupus nephritis. Clin Immunol. 2007, 123: 66-73. 10.1016/j.clim.2006.12.006.CrossRefPubMed
56.
Vallerskog T, Gunnarsson I, Widhe M, Risselada A, Klareskog L, van Vollenhoven R, Malmstrom V, Trollmo C: Treatment with rit-uximab affects both the cellular and the humoral arm of the immune system in patients with SLE. Clin Immunol. 2007, 122: 62-74. 10.1016/j.clim.2006.08.016.CrossRefPubMed
57.
Venigalla RK, Tretter T, Krienke S, Max R, Eckstein V, Blank N, Fiehn C, Ho AD, Lorenz HM: Reduced CD4+, CD25- T cell sensitivity to the suppressive function of CD4+, CD25high, CD127-/low regulatory T cells in patients with active systemic lupus erythematosus. Arthritis Rheum. 2008, 58: 2120-2130. 10.1002/art.23556.CrossRefPubMed
58.
Yates J, Whittington A, Mitchell P, Lechler RI, Lightstone L, Lombardi G: Natural regulatory T cells: number and function are normal in the majority of patients with lupus nephritis. Clin Exp Immunol. 2008, 153: 44-55. 10.1111/j.1365-2249.2008.03665.x.PubMedCentralCrossRefPubMed
59.
Zhao SS, Li XM, Li XP, Zhai ZM, Chen Z, Ma Y, Zhang H, Zheng SG: Expression of CD4+ CD25+CD127(low/-) T cells in patients with systemic lupus erythematosus. Zhonghua Yi Xue Za Zhi. 2008, 88: 453-456.PubMed
60.
Alvarado-Sanchez B, Hernandez-Castro B, Portales-Perez D, Baranda L, Layseca-Espinosa E, Abud-Mendoza C, Cubillas-Tejeda AC, Gonzalez-Amaro R: Regulatory T cells in patients with systemic lupus erythematosus. J Autoimmun. 2006, 27: 110-118. 10.1016/j.jaut.2006.06.005.CrossRefPubMed
61.
Lin SC, Chen KH, Lin CH, Kuo CC, Ling QD, Chan CH: The quantitative analysis of peripheral blood FOXP3-expressing T cells in systemic lupus erythematosus and rheumatoid arthritis patients. Eur J Clin Invest. 2007, 37: 987-996. 10.1111/j.1365-2362.2007.01882.x.CrossRefPubMed
62.
Yan B, Ye S, Chen G, Kuang M, Shen N, Chen S: Dysfunctional CD4+, CD25+ regulatory T cells in untreated active systemic lupus erythematosus secondary to interferon-alpha-producing antigen-presenting cells. Arthritis Rheum. 2008, 58: 801-812. 10.1002/art.23268.CrossRefPubMed
63.
Zhang B, Zhang X, Tang F, Zhu L, Liu Y, Chen W, Lipsky P: Clinical significance of increased CD4+CD25-Foxp3+T cells in patients with new-onset systemic lupus erythematosus. Ann Rheum Dis. 2008, 67: 1037-1040. 10.1136/ard.2007.083543.CrossRefPubMed
64.
Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, Gottlieb PA, Kapranov P, Gingeras TR, Fazekas de St Groth B, Clayberger C, Soper DM, Ziegler SF, Bluestone JA: CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med. 2006, 203: 1701-1711. 10.1084/jem.20060772.PubMedCentralCrossRefPubMed
65.
Franz B, Fritzsching B, Riehl A, Oberle N, Klemke CD, Sykora J, Quick S, Stumpf C, Hartmann M, Enk A, Ruzicka T, Krammer PH, Suri-Payer E, Kuhn A: Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus. Arthritis Rheum. 2007, 56: 1910-1920. 10.1002/art.22699.CrossRefPubMed
66.
Ding D, Mehta H, McCune WJ, Kaplan MJ: Aberrant phenotype and function of myeloid dendritic cells in systemic lupus erythematosus. J Immunol. 2006, 177: 5878-5889.CrossRefPubMed
67.
Decker P, Kotter I, Klein R, Berner B, Rammensee HG: Monocyte-derived dendritic cells over-express CD86 in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2006, 45: 1087-1095. 10.1093/rheumatology/kel061.CrossRef
68.
Koller M, Zwolfer B, Steiner G, Smolen JS, Scheinecker C: Phenotypic and functional deficiencies of monocyte-derived den-dritic cells in systemic lupus erythematosus (SLE) patients. Int Immunol. 2004, 16: 1595-1604. 10.1093/intimm/dxh160.CrossRefPubMed
69.
Tucci M, Quatraro C, Lombardi L, Pellegrino C, Dammacco F, Silvestris F: Glomerular accumulation of plasmacytoid dendritic cells in active lupus nephritis: role of interleukin-18. Arthritis Rheum. 2008, 58: 251-262. 10.1002/art.23186.CrossRefPubMed
70.
Koenen HJ, Smeets RL, Vink PM, Rijssen EV, Boots AM, Joosten I: Human CD25highFoxp3pos regulatory T-cells differentiate into IL-17 producing cells. Blood. 2008, 112: 2340-2352. 10.1182/blood-2008-01-133967.CrossRefPubMed
71.
Tadokoro CE, Shakhar G, Shen S, Ding Y, Lino AC, Maraver A, Lafaille JJ, Dustin ML: Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo. J Exp Med. 2006, 203: 505-511. 10.1084/jem.20050783.PubMedCentralCrossRefPubMed
72.
Tang Q, Adams JY, Tooley AJ, Bi M, Fife BT, Serra P, Santamaria P, Locksley RM, Krummel MF, Bluestone JA: Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat Immunol. 2006, 7: 83-92. 10.1038/ni1289.PubMedCentralCrossRefPubMed
73.
Zhao DM, Thornton AM, DiPaolo RJ, Shevach EM: Activated CD4+CD25+ T cells selectively kill B lymphocytes. Blood. 2006, 107: 3925-3932. 10.1182/blood-2005-11-4502.PubMedCentralCrossRefPubMed
74.
Giroux M, Yurchenko E, St-Pierre J, Piccirillo CA, Perreault C: T regulatory cells control numbers of NK cells and CD8α+ immature dendritic cells in the lymph node paracortex. J Immunol. 2007, 179: 4492-4502.CrossRefPubMed
75.
Terme M, Chaput N, Combadiere B, Ma A, Ohteki T, Zitvogel L: Regulatory T cells control dendritic cell/NK cell cross-talk in lymph nodes at the steady state by inhibiting CD4+self-reactive T cells. J Immunol. 2008, 180: 4679-4686.CrossRefPubMed
76.
Kim YG, Lee CK, Nah SS, Mun SH, Yoo B, Moon HB: Human CD4+CD25+ regulatory T cells inhibit the differentiation of osteoclasts from peripheral blood mononuclear cells. Biochem Biophys Res Commun. 2007, 357: 1046-1052. 10.1016/j.bbrc.2007.04.042.CrossRefPubMed
77.
Zaiss MM, Axmann R, Zwerina J, Polzer K, Guckel E, Skapenko A, Schulze-Koops H, Horwood N, Cope A, Schett G: Treg cells suppress osteoclast formation: a new link between the immune system and bone. Arthritis Rheum. 2007, 56: 4104-4112. 10.1002/art.23138.CrossRefPubMed
78.
Fahlen L, Read S, Gorelik L, Hurst SD, Coffman RL, Flavell RA, Powrie F: T cells that cannot respond to TGF-β escape control by CD4(+)CD25(+) regulatory T cells. J Exp Med. 2005, 201: 737-746. 10.1084/jem.20040685.PubMedCentralCrossRefPubMed
79.
Zheng SG, Wang JH, Stohl W, Kim KS, Gray JD, Horwitz DA: TGF-β requires CTLA-4 early after T cell activation to induce FoxP3 and generate adaptive CD4+CD25+regulatory cells. J Immunol. 2006, 176: 3321-3329.CrossRefPubMed
80.
Alderson KL, Zhou Q, Berner V, Wilkins DE, Weiss JM, Blazar BR, Welniak LA, Wiltrout RH, Redelman D, Murphy WJ: Regulatory and conventional CD4+ T cells show differential effects correlating with PD-1 and B7-H1 expression after immunotherapy. J Immunol. 2008, 180: 2981-2988.PubMedCentralCrossRefPubMed
81.
Ono M, Shimizu J, Miyachi Y, Sakaguchi S: Control of autoimmune myocarditis and multiorgan inflammation by glucocorti-coid-induced TNF receptor family-related protein(high), Foxp3-expressing CD25+and CD25- regulatory T cells. J Immunol. 2006, 176: 4748-4756.CrossRefPubMed
82.
Aswad F, Kawamura H, Dennert G: High sensitivity of CD4+CD25+ regulatory T cells to extracellular metabolites nicotinamide adenine dinucleotide and ATP: a role for P2X7 receptors. J Immunol. 2005, 175: 3075-3083.CrossRefPubMed
83.
Kobie JJ, Shah PR, Yang L, Rebhahn JA, Fowell DJ, Mosmann TR: T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 5'-adenosine monophosphate to adenosine. J Immunol. 2006, 177: 6780-6786.CrossRefPubMed
84.
Krieg AM, Vollmer J: Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity. Immunol Rev. 2007, 220: 251-269. 10.1111/j.1600-065X.2007.00572.x.CrossRefPubMed
85.
Min WP, Zhou D, Ichim TE, Strejan GH, Xia X, Yang J, Huang X, Garcia B, White D, Dutartre P, Jevnikar AM, Zhong R: Inhibitory feedback loop between tolerogenic dendritic cells and regulatory T cells in transplant tolerance. J Immunol. 2003, 170: 1304-1312.CrossRefPubMed
Metadata
Title
Regulatory T cells in systemic lupus erythematosus: past, present and future
Author
David A Horwitz
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 6/2008
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2511

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