Browse > Article

Regulatory T Cell Therapy for Autoimmune Disease  

Ha, Tai-You (Department of Immunology, Chonbuk National University Medical School)
Publication Information
IMMUNE NETWORK / v.8, no.4, 2008 , pp. 107-123 More about this Journal
Abstract
It has now been well documented in a variety of models that T regulatory T cells (Treg cells) play a pivotal role in the maintenance of self-tolerance, T cell homeostasis, tumor, allergy, autoimmunity, allograft transplantation and control of microbial infection. Recently, Treg cell are isolated and can be expanded in vitro and in vivo, and their role is the subject of intensive investigation, particularly on the possible Treg cell therapy for various immune-mediated diseases. A growing body of evidence has demonstrated that Treg cells can prevent or even cure a wide range of diseases, including tumor, allergic and autoimmune diseases, transplant rejection, graft-versus-host disease. Currently, a large body of data in the literature has been emerging and provided evidence that clear understanding of Treg cell work will present definite opportunities for successful Treg cell immunotherapy for the treatment of a broad spectrum of diseases. In this Review, I briefly discuss the biology of Treg cells, and summarize efforts to exploit Treg cell therapy for autoimmune diseases. This article also explores recent observations on pharmaceutical agents that abrogate or enhance the function of Treg cells for manipulation of Treg cells for therapeutic purpose.
Keywords
autoimmune diseases; rapamycin; regulatory T cells; superantigen; suppressor T cells;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Gerber NL, Hardin JA, Chused TM, Steinberg AD: Loss with age in NZB/W mice of thymic suppressor cells in the graft-vs-host reaction. J Immunol 113;1618-1625, 1974   PUBMED
2 Durkin HG, Waksman BH: Thymus and tolerance. Is regulation the major function of the thymus? Immunol Rev 182;33-57, 2001   DOI   ScienceOn
3 Moeller G (Ed): Suppressor T lymphocytes. Transplantation Rev 26;3-205, 1975
4 Mills KH: Regulatory T cells: friend or foe in immunity to infection? Nature Rev Immunol 4;841-855, 2004   DOI   ScienceOn
5 Bluestone JA: Regulatory T-cell therapy: is it ready for the clinic? Nat Rev Immunol 5;343-349, 2005   DOI   ScienceOn
6 Vignail DA, Collison LW, Workman CJ: How regulatory T cell work. Nat Rev Immunol 8;523-532, 2008   DOI   ScienceOn
7 Hayday A, Tigelaar R: Immunoregulation in the tissues by $\gamma$$\delta$T cells. Nat Rev Immunol 3;233-242, 2003   DOI   ScienceOn
8 Morgan ME, van Bilsen JH, Bakker AM, Heemskerk B, Schilham MW, Hartgers FC, Elferink BG, van der Anaden L, De Vies RR, Huizinga TW, Ottenhoff TH, Toes RE: Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans. Human Immunol 66;13-20, 2005
9 Yamaguchi T, Hirota K, Nagahama K, Ohkawa K, Takahashi T, Nomura T, Sakaguchi S: Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity 27;145-159, 2007   DOI   ScienceOn
10 Yamaguchi T, Hirota K, Nagahama K, Ohkawa K, Takahashi T, Nomura T, Sakaguchi S: Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity 27;145-159, 2007   DOI   ScienceOn
11 Nguyen LT, Jacobs J, Mathis D, Benoist C: Where FoxP3-dependent regulatory T cells impinge on the development of inflammatory arthritis. Arthritis Rheum 56;509-520, 2007   DOI   ScienceOn
12 Broere F, Wieten L, Koerkamp EI, van Roon JA, Guichelaar T, Lafeber FP, van Eden W: Oral or nasal antigen induces regulatory T cells that suppress arthritis and proliferation of arthritogenic T cells in joint draining lymph nodes. J Immunol 181;899-906, 2008   DOI
13 Masteller EL, Warner MR, Tang Q, Tarbell KV, McDevitt H, Bluestone JA: Expansion of functional endogenous antien-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice. J Immunol 175;3053-3059, 2005   DOI   PUBMED
14 von Boehmer H: Can studies of tolerance ever lead to therapy? Ann Rheum Dis 65(Suppl 3);iii41-iii43, 2006
15 Wang J, Toes RE: Mechanisms of oral tolerance revisited. Arthritis Res Ther 10;108-109, 2008   DOI   ScienceOn
16 Tritt M, Sgouroudis E, d'Hennezel E, Albanese A, Piccirillo CA: Functional waning of naturally occurring CD4+ regulatory T-cells contributes to the onset of autoimmune diabetes. Diabetes 57;113-123, 2008   DOI   ScienceOn
17 Tiittanen M, Huupponen JT, Knip M, Vaarala O: Insulin treatment in patients with type 1 diabetes induces upregulation of regulatory T-cell markers in peripheral blood mononuclear cells stimulated with insulin in vitro. Diabetes 55;3446-3454, 2006   DOI   ScienceOn
18 Jaeckel E, von Boehmer H, Manns MP: Antigen-specific FoxP3-transduced T-cells can control established type 1 diabetes. Diabetes 54;306-310, 2005   DOI
19 Noris M, Casiraghi F, Todeschini M, Cravedi P, Cugini D, Monteferracnte G, Aiello S, Cassis L, Gotti E, Gaspari F, Cattaneo D, Perico N, Remuzzi G: Regulatory T cells and T cell depletion: role of immunosuppressive drugs. J Am Soc Nephrol 18;1007-1018, 2007   DOI   ScienceOn
20 Wolf D, Hochgger K, Wolf AM, Rumpold HF, Gastl G, Tilg H, Mayer G, Gunsilius E, Rsenkranz AR: CD4+CD25+ regulatory T cells inhibit experimental anti-glomerular basement membrane glomerulonephritis in mice. J Am Soc Nephrol 16;1360-1370, 2005   DOI   ScienceOn
21 Kang HK, Michaels MA, Berner BR, Datta SK: Very low-dose tolerance with nucleosomal peptides controls lupus and induces potent regulatory T cell subsets. J Immunol 174;3247-3255, 2005   DOI   PUBMED
22 Mekal DJ, Alli RS, Geiger TL: IL-10-dependent infectious tolerance after the treatment of experimental allergic encephalomyelitis with redirected CD4+CD25+ T lymphocytes. Proc Natl Acad Sci USA 102;11817-11822, 2005
23 Venken K, Hellings N, Broekmans T, Hensen K, Rummens JL, Stinissen P: Natural naive CD4+CD25+ $CD127^{low}$ regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression. J Immunol 180;6411-6420, 2008   DOI   PUBMED
24 Azba NA, Bassyoun IH, Emad Y, Abd El-Wahab GA, Hamdy G, Mashahit MA: CD4+CD25+ regulatory T cells (TREG) in systemic lupus erythematousus (SLE) patients: the possible influence of treatment with corticosteroids. Clin Immunol 127;151-157, 2008   DOI   ScienceOn
25 Parietti V, Chifflot M, Muller S, Monneaux F: Regulatory T cells and systemic lupus erythematosus. Ann N Y Acad Sci 1108;64-75, 2007   DOI   ScienceOn
26 Kang HK, Datta SK: Regulatory T cells in lupus. Int Rev Immunol 25;5-25, 2006   DOI   ScienceOn
27 Saruta M, Yu QT, Fleshner PR, Mantel PY, Schmidt-Weber CB, Banham AH, Papadakis KA: Characterization of FOXP3+CD4+ regulatory T cells in Crohn's disease. Clin Immunol 125;281-290, 2007   DOI   ScienceOn
28 Aricha R, Feferman T, Fuchs S, Souroujon MC: Ex vivo generated regulatory T cells modulate experimental autoimmune myasthenia gravis J Immunol 180;2132-2139, 2008   DOI
29 Isaacs JD: Therapeutic T-cell manipulation in rheumatoid arthritis: past, present and future. Rheumatology (Oxford) 47;1461-1468, 2008   DOI   ScienceOn
30 Sheng JR, Li L, Ganesh BB, Vasu C, Prabhakar BS, Meriggioli MN: Regulatory T cells induced by GM-CSF suppress ongoing experimental myasthenia gravis. Clin Immunol 128;172-180, 2008   DOI   ScienceOn
31 Meriggioli MN, Sheng JR, Li L, Prabhakar BS: Strategies for treating auto immunity: novel insights from experimental myasthenia gravis. Ann N Y Acd Sci 1132;276-282, 2008   DOI   ScienceOn
32 Gang E, Vasu C, Cheatem D, Prabhakar BS: IL-10-producing CD4+CD25+ regulatory T cells play a critical role in granulocyte-marcrophage colony-stimulating factor-induced suppression of experimental autoimmune thyroiditis. J Immunol 174;7006-7013, 2005   DOI   PUBMED
33 Chorny A, Gonzales-Rey E, Ganea D, Delgado M: Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo: therapeutic applications in autoimmunity and transplantation. Ann NY Acad Sci 1070;190-195, 2006   DOI   ScienceOn
34 O'connor RA, Anderton SM: Foxp3+ regulatory T cells in the control of experimental CNS autoimmune disease. J Neuroimmunol 193;1-11, 2008   DOI   ScienceOn
35 Venken K, Hellings N, Broekmans T, Hensen K, Rummens JL, Stinissen P: Natural naive CD4+CD25+ CD127low regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression. J Immunol 180;6411-6420, 2008   DOI
36 Delgado M, Chorny A, Gonazalez-Rey E, Ganea D: Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo. J Leukc Biol 78;1327-1338, 2005   DOI   ScienceOn
37 Ha TY, Waksman BH, Treffers HP: Thymic suppressor cell. I. Separation of subpopulation with suppressor activity. J Exp Med 139;13-23, 1974   DOI   ScienceOn
38 Ziegler SE: FOXP3: of mice and men. Ann Rev Immunol 24;209-226, 2006   DOI   ScienceOn
39 Suvas S, Kumaraguru U, Pack CD, Lee S, Rouse BT: CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses. J Exp Med 198;889-901, 2003   DOI   ScienceOn
40 Ha TY, Park YM, Park YK, Lee HK, Park CW: Regulation of cellular immunity in cryptococosis. III. Induction of Cryptococcus neoformans-specific T cells and hybridoma. Korean J Immunol 14;15-23, 1992
41 0Kelchtemans H, Geboes L, Mitera T, Huskens D, Leclercq G, Matthys P: Activated CD4+CD25+ regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis. Ann Rheum Dis 2008
42 Forger F, Marcoli N, Gadika S, Moller B, Villiger PM, Ostensen M: Pregnancy induces numerical and functional changes of $CD4+CD25^{high}$ regulatory T cells in patients with rheumatoid arthritis. Ann Rheum Dis 67;984-990, 2008   DOI   ScienceOn
43 Cao D, van Vollenhoven R, Klareskog L, Trollmo C, Malmstrom V: CD25brightCD4+ regulatory T cells are enriched in inflamed joints of patients with chronic rheumatic disease. Arthritis Res Ther 6;R335-R346, 2004   DOI   ScienceOn
44 Char JG, Coe D, Chen D, Simpson E, Dyson J, Scott D: in vitro expansion improves in vivo regulation by CD4+CD25+ regulatory T cells. J Immunol 180;858-869, 2008   DOI
45 Suarez A, Lopez P, Gomez J, Gutierrez C: Enrichment of CD4+CD25high T cell population in SLE patients treated with glucocorticoids. Ann Rheum Dis 65;1512-1517, 2006   DOI   ScienceOn
46 Reynolds AD, Banerjee R, Liu J, Gendelman HE, Mosley RL: Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease. J Leukoc Biol 82;1083-1094, 2007   DOI   ScienceOn
47 Gonzalez-Rey E, Fernandez-Martin A, Chorney A, Delgado M: Vasoactive intestinal peptide induces CD4+, CD25+ T regulatory cells with therapeutic effect in collagen-induced arthritis. Arthritis Rheum 54;864-876, 2006   DOI   ScienceOn
48 Baecher-Allan C, Hafler DA: Suppressor T cells in human diseases. J Exp Med 200;273-276, 2004   DOI   ScienceOn
49 Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z, Shimizu J, Takahashi T, Nomura T: Fox3+CD25+CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev 212;8-27, 2006   DOI   ScienceOn
50 Stummvoll GH, DiPaolo RJ, Huter EN, Davidson TS, Glass D, Ward JM, Shevach EM: Th1, Th2, and Th17 effector T cell-induced autoimmune gastritis differs in pathological pattern and in susceptibility to suppression by regulatory T cells. J Immunol 181;1908-1916, 2008   DOI
51 Mekala DJ, Geiger TL: Immunotherapy of autoimmune encephalomyelitis with redirected CD4+CD25+ T lymphocytes. Blood 105;2090-2092, 2005   DOI   ScienceOn
52 Tada T, Taniguchi M, Takemori T: Properties of primed suppressor T cells and their products. Transplant Rev 26;106-129, 1975   PUBMED
53 Rouse BT, Sehrawat S: Regulatory T cells and infectious disease. Immune Network 7;167-172, 2007   과학기술학회마을   DOI
54 Basten A, Fazekas de St Groth B: Special regulatory T-cell review: T cell dependent suppression revisited. Immunol 123;33-39, 2008   DOI   ScienceOn
55 Sakaguchi S, Powrie F: Emerging challenges in regulatory T cell function and biology. Science 317;627-629, 2007   DOI   ScienceOn
56 Ochoa-Reparaz J, Riccardi C, Rynda A, Jun S, Callis G, Pascual DW: Regulatory T cell vaccination without autoantigen protects against experimental autoimmune encephalomyelitis. J Immunol 178;1791-1799, 2007   DOI
57 Verginis P, Li HS, Carayanniotis G: Tolerogenic semimature dendritic cells suppress experimental autoimmune thyroiditis by activation of thyroglobulin-specific CD4+ CD25+ T cells. J Immunol 174;7433-7439, 2005   DOI   PUBMED
58 Zozulya AL, Wiendl H: The role of regulatory T cells in multiple sclerosis. Nat Clin Prat Neurol 4;384-398, 2008   DOI   ScienceOn
59 Coleman CA, Muller-Trutwin MC, Apetrei C, Pandrea I: T regulatory cells: aid or hindrance in the clearance of disease? J Cell Mol Med 11;1291-1325, 2007   DOI   ScienceOn
60 Nguyen LT, Jacobs J, Mathis D, Benoist C: Where FoxP3-dependent regulatory T cells impinge on the development of inflammatory arthritis. Arthritis Rheum 56;509-520, 2007   DOI   ScienceOn
61 Radbruch A, Thiel A: Cell therapy for autoimmune diseases: does it have a future? Ann Rheumatic Dis 63(Suppl 2);ii96-ii101, 2004
62 Godebu E, Summers-Torres D, Lin MM, Baaten BJ, Bradley LM: Polyclonal adaptive regulatory CD4 cells that can reverse type 1 diabetes become oligoclonal long-term protective memory cells. J Immunol 181;1798-1805, 2008   DOI
63 Gershon RK, Kondo K: Infectious immunological tolerance. Immunology 21;903-914, 1971   PUBMED
64 Shevach EM: D4+: CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol 182;389-400, 2002
65 Sarkar S, Fox DA: Regulatory T cell defects in rheumatoid arthritis. Arthritis Rheum 56;710-713, 2007   DOI   ScienceOn
66 Kohm AP, Carpentier PA, Anger HA, Miller SD: Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J Immunol 169;4712-4716, 2002   DOI   PUBMED
67 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-TNF$\alpha$ therapy. J Exp Med 200;277-285, 2004   DOI   ScienceOn
68 Tang Q, Henriksen KJ, Bi M, Finger EB, Szot G, Ye J, Masteller EL, McDevitt H, Bonyhadi M, Bluestone JA: in vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J Exp Med 199;1455-1465, 2004   DOI   ScienceOn
69 Chin KM, Foss FM: Biologic correlates of response and survival in patients with cutaneous T cell lymphoma treated with denileukin diftitox. Clin Lymphoma Myeloma 7;199-204, 2006   DOI   ScienceOn
70 Cao D, Boerjesson O, Larsson P, Rudin A, Gunnarsson I, Klareskog L, Malmstroem V, Trollmo C: FOXP3 identifies regulatory $CD25^bright$ CD4+ T cells in rheumatic joints. Scand J Immunol 63;444-452, 2006   DOI   ScienceOn
71 Saresella M, Marventano I, Longhi R, Trabattoni D, Mendozzi L, Caputo D, Clerici M: CD4+CD25+Fox3+ PD-regulatory T cells in acute and stable elapsing-remitting multiple sclerosis and their modulation by therapy. FASEB 22;3500-3508, 2008   DOI   ScienceOn
72 Anderton SM, Liblau RS: Regulatory T cells in the control of inflammatory demyelingating diseases of the central nervous system. Curr Opin Neurol 21;248-254, 2008   DOI   ScienceOn
73 Denning TL, Kim G, Kronenberg M: Cutting edge: CD4+CD25+ regulatory T cells impaired for intestinal homing can prevent colitis. J Immunol 174;7487-7491, 2005   DOI   PUBMED
74 McLachlan SM, Nagayama Y, Pichurin PN, Mizutori Y, Chen CR, Misharin A, Aliesk HA, Rapopori B: The link between Graves' disease and Hashimoto's thyroiditis: a role for regulatory T cells. Endocrinology 148;5724-5733, 2007   DOI   ScienceOn
75 Delgado M, Toscano MG, Benabedellah K, Cobo M, O'Valle F, Gonzales-Rey E, Matin F: in vivo delivery of lentiviral vectors expressing vasoactive intestinal peptide complementary DNA as gene therapy for collagen-induced arthritis. Arthritis Rheum 58;1026-1037, 2008   DOI   ScienceOn
76 Battaglia M, Stabilini A, Migliavacca B, Horejs-Hoeck J, Kaupper T, Roncarolo MG: Rapamycin promotes expansion of functional CD4+CD25+ FOXP3+ regulatory T cells of both healthy subject and type 1 diabetic patients. J Immunol 177;8338-8347, 2006   DOI
77 Ha TY, Kim HI, Im SY: Effect of dexamethasone on different types of murine T suppressor cells. Korean J Immunol 9;1-15, 1987
78 Hawrylowicz CM: Regulatory T cells and IL-10 in allergic inflammation. J Exp Med 202;1459-1463, 2005   DOI   ScienceOn
79 LaCava A: T-regulatory cells in systemic lupus erythematosus. Lupus 17;421-425, 2008   DOI
80 Mottet C, Uhlig HH, Powrie F: cutting edge: cure of colitis by CD4+CD25+ regulatory T cells. J Immunol 170; 3939-3943, 2003   DOI   PUBMED
81 Solomou ED, Rezvan K, Mielke S, Malide D, Keyvanfar K, Visconte V, Kajigaya S, Barrett AJ, Young NS: Deficient CD4+CD25+FOXP3+ T regulatory cells in acquired aplastic anemia. Blood 110;1603-1606, 2007   DOI   ScienceOn
82 Uhlig HH, Coombes J, Mottet C, Izcue A, Thompson C, Fanger A, Tannapfel A, Fontenof JD, Ramsdell F, Powrie F: Characterization of Foxp3+ CD4+CD25+ and IL-10-secreting CD4+CD25+ T cells during cure of colitis. J Immunol 177;5852-5860, 2006   DOI
83 Ha TY, Waksman BH: Role of the thymus in tolerance .X. 'Suppressor' activity of antigen-stimulated rat thymocytes transferred to normal recipients. J Immunol 110;1290-1299, 1973   PUBMED
84 Bacchetta R, Gambineri E, Roncarolo MG: Role of regulatory T cells and FOXP3 in human diseases. J Allergy Clin Immunol 120;227-235, 2007   DOI   ScienceOn
85 Mahajan D, Wang Y, Qin X, Wang Y, Zheng G, Wang YM, Alexander SI, Harris DC: CD4+CD25+ regulatory T cell protect against injury in an innate murine model of chronic kidney disease. J Am Soc Nephrol 17;2731-2741, 2006   DOI   ScienceOn
86 Selvaraj RK, Geiger TL: Mitigation of experimental allergic encephalomyelitis by TGF-$\beta$ induced Foxp3+ regulatory T lymphocytes through the induction of anergy and infectious tolerance. J Immunol 180;2830-2838, 2008   DOI
87 Danese S, Rutella S: The Janus faces of CD4+CD25+ regulatory T cells in cancer and autoimmunity. Curr Med Chem 14;649-666, 2007   DOI   ScienceOn
88 Wang J, Toes RE: Mechanisms of oral tolerance revisited. Arthritis Res Ther 10;108-109, 2008   DOI   ScienceOn
89 Karagiannidis C, Akdis M, Holopainen P, Wooley NJ, Hense G, Ruckert B, Mantel PY, Menz G, Akdis CA, Blasser K, Schmidt-Weber CB. Glucoorticoids upregulated FOXP3 expression and regulatory T cells in asthma. J Allergy Clin Immunol 114;1425-1433, 2004   DOI   ScienceOn
90 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 mechanisms of self-tolerance causes various autoimmune diseases. J Immunol 155;1151-1164, 1995   PUBMED
91 Hori S, Sakaguchi S: Foxp3: a critical regulator of the development and function of regulatory T cells. Microbes Infect 6;745-751, 2004   DOI   ScienceOn
92 Gonzalez-Rey E, Fernandex-Martin A, Chorny A, Martin J, Pozo D, Ganea D, Delgado M: Therapeutic effect of vasoactive intestinal peptide on experimental autoimmune encephalomyelitis; down-regulaltion of inflammatory and autoimmune responses. Am J Pathol 168;1179-1188, 2006   DOI   ScienceOn
93 Battaglia M, StabiliniA, Roncarolo MG: Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood 105;4743-4748, 2005   DOI   ScienceOn
94 Ou LS, Goleva E, Hall C, Leung DT: T regulatory cells in atopic dermatitis and subversion of their activity by superantigens. J Allergy Clin Immunol 113;756-763, 2004   DOI   ScienceOn
95 Beyer M, Schultze JL: Regulatory T cells in cancer. Blood 1108;804-811, 2006
96 Salma AD, Chaudhry AN, Holthaus KA, Mosley K, Kalluri R, Sayegh MH, Lecler RI, Pusey CD, Lightstone L: Regulation by CD25+ lymphocytes of autoantigen-specific T-cell responses in Goodpasture's (anti-GBM) disease. Kidney Int 64;1685-1694, 2003   DOI   ScienceOn
97 Wang J, Takeuchi H, Sonobe Y, Jin S, Mizuno T, Miyakawa S, Fujiwara M, Nakamura Y, Kato T, Muramatsu H, Muramasu T, Suzumura A: Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population. Proc Natl Acad Sci U S A 105;3915-3920, 2008
98 Zheng SG, Wang JH, Koss MN, Quisomorio F Jr, Gray JD, Horwitz DA: CD4+ and CD8+ regulatory T cells generated ex vivo with IL-2 and TGF-beta suppress a stimulatory graft-versus-host disease with a lupus-like syndrome. J Immunol 172;1531-1539, 2004   DOI   PUBMED
99 Mitrrucker HW, Kaufmann HE: Mini-review: regulatory T cells and infection: suppression revisited. Eur J Immunol 34;306-312, 2004   DOI   ScienceOn
100 Tang Q, Bluestone JA: The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol 9; 239-244, 2008   DOI   ScienceOn
101 Que-Gewirth NS, Sullenger BA: Gene therapy progress and prospects: RNA aptamers. Gene Ther 14;283-291, 2007   DOI   ScienceOn
102 Nardekku DT, Cloute JP, Luk KH, Torrealba J, Warner TF, Callister SM, Schell RF: CD4(+)CD25(+) T cells prevent arthritis associated with Borrelia vaccination and infection. Clin Diag Lab Immunol 12;786-792, 2005
103 Ochoa-Reparaz J, Rynda A, Ascon MA, Yang X, Kochetkova I, Riccardi C, Callis G, TrunkleT, Pascual DW: IL-13 production by regulatory T cells protects against experimental autoimmune encephalomyelitis independently of autoantigen. J Immunol 181;954-968, 2008   DOI
104 Coombes JL, Maloy KJ: Control of intestinal homeostasis by regulatory T cells and dendritic cells. Seminars Immunol 19;116-126, 2007
105 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 65;553-554, 2006   DOI   ScienceOn
106 Bruder D, Probst-Kepper M, Westendorf AM, Geffers R, Beissert S, Loser K, von Boehmer H, Buer J, Hansen W: Neuropilin-1: a surface marker of regulatory T cells. Eur J Immunol 34;623-630, 2004   DOI   ScienceOn
107 Leipe J, Skapenko A, Lipsky PE, Schulze-Koops H: Regulatory T cells in rheumatoid arthritis. Arthritis Res Ther 7;93, 2005   DOI   ScienceOn
108 Lee VW, Wang YM, Wnag YP, Zheng D, Polhill T, Cao Q, Wu H, Alexander IE, Alexander SI, Harris DC: Regulatory immune cells in kidney disease. Am J Physiol Renal Physiol 295;F335-F342, 2008   DOI   ScienceOn
109 Ford McIntyre MS, Young KJ, Gao J, Joe B, Zhang L: Cutting edge: in vivo trogocytosis as a mechanism of double negative regulatory T cell-mediated antigen-specific suppression. J Immunol 181;2271-2275, 2008   DOI
110 Ha TY, Chung HT: Effect of cyclophosphamide on humoral and cellular immune response in mice. J Korean Med Ass 20;985-994, 1977
111 Chen ML, Yan BS, Bando Y, Kuchroo VK, Weiner HL: Latency-associated peptide identifies a novel CD4+CD25+ regulatory T cell subset with TGF beta-mediated function and enhanced suppression of experimental autoimmune encephalomyelitis. J Immunol 180;7327-7337, 2008   DOI   PUBMED
112 Glinka Y, Pud'homme GJ: Neruopilin-1 is a receptor for transforming growth factor $\beta$-1, activates its latent form, and promotes regulatory T cell activity. J Leukoc Biol 84;302-310, 2008   DOI   ScienceOn
113 Sakaguchi S, Fukuma K, Kuribayashi K, Masuda T: Organ-specific autoimmune disease induced in mice by elimination of T-cell subset. I. Evidence for the active participation of T-cells in natural self-tolerance: deficit of a T-cell subset as a possible cause of autioimmune disease. J Exp Med 161;72-87, 1985   DOI
114 Sarkar S, Fox DA: Regulatory T cell defects in rheumatoid arthritis. Arthritis Rheum 56;710-713, 2007   DOI   ScienceOn
115 Goleva E, Cardona ID, Ou LS, Leung DY.: Factors that regulate naturally occurring T regulatory cell-mediated suppression. J Allergy Clin Immunol 116;1000-1094, 2005   DOI   ScienceOn
116 Forger F, Marcoli N, Gadika S, Moller B, Villiger PM, Ostensen M: Pregnancy induces numerical and funtinal changes of $CD4+CD25^{high}$ regulatory T cells in patients with rheumatoid arthritis. Ann Rheum Dis 67;984-990, 2008   DOI   ScienceOn
117 Stein-Streilein J, Taylor AW: An eye's view of T regulatory cells. J Leukoc Biol 81;593-598, 2007   DOI   ScienceOn
118 Sakaguchi S, Powrie F: Emerging challenges in regulatory T cell function and biology. Science 317;627-629, 2007   DOI   ScienceOn
119 Stein-Streilein J, Taylor AW: An eye's view of T regulatory cells. J Leukoc Biol 81;593-598, 2007   DOI   ScienceOn
120 Park MJ, Min SY, Park KS, Cho YG, Cho ML, Jung YK, Park HY, Chang SH, Cho SG, Min JK, Park SH, Kim HY: Indoleamine 2,3-dioxygenase-expresssing dendritic cells are involved in the generation of CD4+CD25+ regulatory T cells in Peyer's patches in an orally tolerized, collagen-induced arthritis mouse model. Arthritis Res Ther 10;R11, 2008   DOI   ScienceOn
121 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) 47;789-794, 2008   DOI   ScienceOn
122 Bendelac A, Savage PB, Teyton L: The biology of NKT cells. Ann Rev Immunol 25;297-336, 2007   DOI   ScienceOn
123 Delgado M, Chorny A, Gonzales-Rey E, Ganea D: Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo. J Leukc Biol 78;1327-1338, 2005   DOI   ScienceOn
124 Ha TY, Waksman BH, Treffers HP: The thymic suppressor cell. II. Metabolic requirement of suppressor activity. Immunol Commun 3;351-359, 1974   DOI   PUBMED
125 Gershon RK, Eardley DD, Durum S, Green R, Shen FW, Yamauci K, Cantor H, Murphy DB: Contrasuppression. A novel immunoregulatory activity. J Exp Med 153;1533-1546, 1981   DOI
126 Waksman BH: Tolerance, the thymus, and suppressor T cells. Clin Exp Immunol 28;363-374, 1977   PUBMED
127 Jiang S, Lechler RI: CD4+CD25+regulatory T-cell therapy for allergy, autoimmune and transplant rejection. Inflamm Allergy Drug Targets 5;239-242, 2006   DOI
128 Young KJ, DuTemple B, Phillips MJ, Zhang L: Inhibition of graft versus host disease by double negative regulatory T cells. J Immunol 171;134-141, 2003   DOI   PUBMED
129 Wang YM, Zhang GY, Wang Y, Hu M, Wu H, Watson D, Hori S, Alexander IE, Harris DC, Alexander SI: Foxp3-transduced polyclonal regulatory T cells protect against chronic renal injury from adriamycin. J Am Soc Nephrol 17;697-706, 2006   DOI   ScienceOn
130 Dejaco C, Duftner C, Grubeck-Loebsenstein B, Schirmer M: Imbalance of regulatory T cells in human autoimmune diseases. Immunology 117;289-300, 2006   DOI   ScienceOn
131 Kelchtemans H, Geboes L, Mitera T, Huskens D, Leclercq G, Matthys P: Activated CD4+CD25+ regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis. Ann Rheum Dis doi:10.1136, 14 May 2008
132 Braat H, McGuirk P, Ten Kate FJ, Hubiregtse I, Dunne PJ, Hommes D, Van Deventer SJ, Mills KH: Prevention of experimental colitis by parenteral administration of a pathogen-derived immunomodulatory molecule. Gut 56; 351-357, 2007   DOI   ScienceOn
133 Tarbell KV, Yamazaki S, Olson K, Toy P, Steinman RM: CD25+CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J Exp Med 199;1467-1477, 2004   DOI   ScienceOn
134 Venken K, Hellings N, Thewissen M, Somers V, Hensen K, Rummens JL, Medaer R, Hupperts R, Stinissen P: Compromised CD4+CD25high regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 exxpression at the single-cell level. Immunology 123;79-89, 2008   DOI   ScienceOn
135 Young NS, Scheinberg P, Calado RT: Aplastic anemia: Curr Opin Hematol 15;162-168, 2008   DOI   ScienceOn
136 Broere F, Wieten L, Koerkamp EI, van Roon JA, Guichelaar T, Lafeber FP, van Eden W: Oral or nasal antigen induces regulatory T cells that suppress arthritis and proliferation of arthritogenic T cells in joint draining lymph nodes. J Immunol 181;899-906, 2008   DOI
137 Mira E, Leon B, Barber DF, Jimenez-Baranda S, Goya I, Almonacid L, Marquez G, Zaballos A, Martinex-A C, Stein JV, Ardavin C, Manes S: Statins induce regulatory T cell recruitment via CCL1 dependent pathway. J Immunol 181;3524-3534, 2008   DOI
138 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-TNF $\alpha$ therapy. J Exp Med 200;277-285, 2004   DOI   ScienceOn
139 Zhang C, Zhang J, Tian Z: 2006. The regulatory effect of natural killer cells: do 'NK-reg cells' exist? Cell Mol Immunol 3;241-254, 2006
140 Behrens F, Himsel A, Rehart S, Stanczyk J, Beutel B, Zimmermann SY, Koehl U, Moeller B, Gay S, Kaltwasser JP, Pfeilschifter JM, Radkeke HH: Imbalance in distribution of functional autologous regulatory T cells in rheumatoid arthritis. Ann Rheum Dis 66;1151-1156, 2007   DOI   ScienceOn
141 Richer MJ, Straka N, Fang D, Shanina I, Horwitz MS: Regulatory T-cells protect from type 1 diabetes after induction by Coxsackievirus infection in the context of transforming growth factor-$\beta$. Diabetes 57;1302-1311, 2008   DOI   ScienceOn
142 Proft T, Fraser JD: Bacterial superantigens. Clin Exp Immunol 133;299-306, 2003   DOI
143 Feunou P, Vanwetswinkel S, Gaudray F, Goldman M, Matthys P, Braun MY: Foxp3+CD25+T regulatory cells stimulate IFN-gamma-independent CD152-mediated activation of tryptophan catabolisms that provides dendritic cells with immune regulatory activity in mice unresponsive to staphylococcal enterotoxin B. J Immunol 179;910-917, 2007   DOI   PUBMED
144 Thomson CW, Lee BP, Zhang L: Double-negative regulatory T cells: non-conventional regulators. Immunol Res 35;163-178, 2006   DOI
145 Dorf ME, Benaceraf B: Suppressor cells and immunoregulation. Ann Rev Immunol 2;127-158, 1984   DOI   ScienceOn
146 Valencia X, Yarboro C, Illei G, Lipsky PE: Deficient CD4+CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J Immunol 178;2579-2588, 2007   DOI
147 Gershon RK, Cohen P, Hencin,R, Liebhaber SA: Suppressor T cells. J Immunol 108;586-590, 1972   PUBMED
148 Sakaguchi S: Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Ann Rev Immunol 22;531-562, 2004   DOI   ScienceOn
149 Kang SM, Tang Q. Bluestone JA: CD4+CD25+ regulatory T cells in transplantation: progress, challenges and prospects. Am J Transplant 7;1457-1463, 2007   DOI   ScienceOn
150 Venken K, Hellings N, Thewissen M, Somers V, Hensen K, Rummens JL, Medaer R, Hupperts R, StinissenP: Compromised CD4+CD25high regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level. Immunology 123;79-89, 2008   DOI   ScienceOn
151 Gregori S, Giarratana N, Smiroldo S, Adorini L: Dynamics of pathogenic and suppressor T cells in autoimmune diabetes development. J Immunol 171;4040-4047, 2003   DOI   PUBMED
152 Gambinen E, Torgenson T, Ochs HD: Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Reumatol 15;430-435, 2003   DOI   ScienceOn
153 Liu MF, Wang CR, Fung LL, Lin LH, Tsai CN: The presence of cytokine-suppressive CD4+CD25+ T cells in the peripheral blood and synovial fluid of patients with rheumatoid arthritis. Scand J Immunol 62;312-317, 2005   DOI   ScienceOn
154 Morgan ME, Flierman R, van Duivenvoorde M, Witteveen HJ, van Ewijk W, van Laar JM, de Vries RR, Toes RE: Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells. Arthritis Rheum 52;2212-2221, 2005   DOI   ScienceOn
155 Kanagawa O, Militech A, Vaupel BA: Regulation of diabetes development by regulatory T cells in pancreatic islet antigen-specific TCR transgenic nonobese diabetic mice. J Immunol 168;6159-6164, 2002   DOI   PUBMED
156 DiPaola RJ, Glass DD, Bijwaard, KE, Shevach EM: CD4+CD25+T cells prevent the development of organ-specific autoimmune disease by inhibiting the differentiation of autoreactive effector T cells. J Immunol 175;7135-7142, 2005   DOI   PUBMED