Browse > Article

Peripheral Generation of $CD4^+CD25^+Foxp3^+$ Regulatory T Cells  

Kim, Byung-Seok (Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University)
Park, Young-Jun (Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University)
Kang, Chang-Yuil (Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University)
Publication Information
IMMUNE NETWORK / v.7, no.1, 2007 , pp. 1-9 More about this Journal
Abstract
[ $CD4^+CD25^+$ ] regulatory T cells (Tregs) expressing the lineage-specific marker Foxp3 represent an important regulatory T cell that is essential for maintaining peripheral tolerance. Although it was believed that Treg development is solely dependent on the thymus, accumulating evidence demonstrates that Tregs can also be induced in the periphery. Considering the various origins of peripherally developed $CD4^+CD25^+Foxp3^+$ regulatory T cells, it seems likely that multiple factors are involved in the peripheral generation of Tregs.
Keywords
$CD4^+CD25^+Foxp3^+$ regulatory T cell; development; generation;
Citations & Related Records
연도 인용수 순위
  • Reference
1 van Parijs L, Perez VL, Abbas AK: Mechanisms of peripheral T cell tolerance. Novartis Found Symp 215;5-14, 1998
2 Piccirillo CA, Shevach EM: Naturally-occurring CD4+ CD25+ immunoregulatory T cells: central players in the arena of peripheral tolerance. Semin Immunol 16;81-88, 2004   DOI   ScienceOn
3 Wing K, Suri-Payer E, Rudin A: CD4+ CD25+-regulatory T cells from mouse to man. Scand J Immunol 62;1-15, 2005   PUBMED
4 Hori S, Nomura T, Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3. Science 299;1057-1061, 2003   DOI   ScienceOn
5 Fontenot JD, Gavin MA, Rudensky AY: Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nat Immunol 4;330-336, 2003   DOI   ScienceOn
6 Mills KH: Regulatory T cells: friend or foe in immunity to infection? Nat Rev Immunol 4;841-855, 2004   DOI   ScienceOn
7 Taams LS, Akbar AN: Peripheral generation and function of CD4+ CD25+ regulatory T cells. Curr Top Microbiol Immunol 293;115-131, 2005   DOI
8 Akbar AN, Vukmanovic-Stejic M, Taams LS, Macallan DC: The dynamic co-evolution of memory and regulatory CD4+ T cells in the periphery. Nat Rev Immunol 7;231-237, 2007   DOI   ScienceOn
9 Curotto de Lafaille MA, Lino AC, Kutchukhidze N, Lafaille JJ: CD25- T cells generate CD25+ Foxp3+ regulatory T cells by peripheral expansion. J Immunol 173;7259-7268, 2004   DOI   PUBMED
10 Knoechel B, Lohr J, Kahn E, Bluestone JA, Abbas AK: Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen. J Exp Med 202;1375-1386, 2005   DOI   ScienceOn
11 Liang S, Alard P, Zhao Y, Parnell S, Clark SL, Kosiewicz MM: Conversion of CD4+ CD25- cells into CD4+ CD25+ regulatory T cells in vivo requires B7 costimulation, but not the thymus. J Exp Med 201;127-137, 2005   DOI   ScienceOn
12 Almeida ARM, Zaragoza B, Freitas AA: Competition controls the rate of transition between the peripheral pools of CD4+CD25- and CD4+CD25+ T cells. Int Immunol 18;1607-1613, 2006   DOI   ScienceOn
13 Park HB, Paik DJ, Jang E, Hong S, Youn J: Acquisition of anergic and suppressive activities in transforming growth factor-beta-costimulated CD4+CD25- T cells. Int Immunol 16;1203-1213, 2004   DOI   ScienceOn
14 Walker MR, Carson BD, Nepom GT, Ziegler SF, Buckner JH: De novo generation of antigen-specific CD4+CD25+ regulatory T cells from human CD4+CD25- cells. Proc Natl Acad Sci USA 102;4103-4108, 2005
15 Zheng SG, Wang J, Wang P, Gray JD, Horwitz DA: IL-2 is essential for TGF-beta to convert naive CD4+Cd25- Cells to CD25+Foxp3+ Regulatory T Cells and for Expansion of These Cells. J Immunol 178;2018-2027, 2007   DOI
16 Ziegler SF: FOXP3: not just for regulatory T cells anymore. Eur J Immunol 37;21-23, 2007   DOI   ScienceOn
17 Ostlie N, Milani M, Wang W, Okita D, Conti-Fine BM: Absence of IL-4 facilitates the development of chronic autoimmune myasthenia gravis in C57BL/6 mice. J Immunol 170;604-612, 2003   DOI   PUBMED
18 Setoguchi R, Hori S, Takahashi T, Sakaguchi S: Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med 201; 723-735, 2005   DOI   ScienceOn
19 Coutinho A, Hori S, Carvalho T, Caramalho I, Demengeot J: Regulatory T cells: the physiology of autoreactivity in dominant tolerance and 'quality control' of immune responses. Immunol Rev 182;89-98, 2001   DOI   ScienceOn
20 Wing K, Sakaguchi S: Regulatory T cells as potential immunotherapy in allergy. Curr Opin Allergy Clin Immunol 6; 482-488, 2006   DOI   ScienceOn
21 Ahern DJ, Robinson DS: Regulatory T cells as a target for induction of immune tolerance in allergy. Curr Opin Allergy Clin Immunol 5;531-536, 2005   DOI   ScienceOn
22 Wing K, Ekmark A, Karlsson H, Rudin A, Suri-Payer E: Characterization of human CD25+ CD4+ T cells in thymus, cord and adult blood. Immunology 106;190-199, 2002   DOI   ScienceOn
23 Willenborg DO, Fordham S, Bernard CC, Cowden WB, Ramshaw IA: IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. J Immunol 157;3223-3227, 1996   PUBMED
24 Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M:Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155;1151-1164, 1995   PUBMED
25 Miller JFAP, Heath WR: Self-ignorance in the peripheral T-cell pool. Immunol Rev 133;131-150, 1993   DOI   ScienceOn
26 Kretschmer K, Apostolou I, Hawiger D, Khazaie K, Nussenzweig MC, von Boehmer H: Inducing and expanding regulatory T cell populations by foreign antigen. Nat Immunol 6;1219-1227, 2005   DOI   ScienceOn
27 Mucida D, Kutchukhidze N, Erazo A, Russo M, Lafaille JJ, Curotto de Lafaille MA: Oral tolerance in the absence of naturally occurring Tregs. J Clin Invest 115;1923-1933, 2005   DOI   ScienceOn
28 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 212;8-27, 2006   DOI   ScienceOn
29 Wood KJ, Sakaguchi S: Regulatory T cells in transplantation tolerance. Nature Reviews Immunology 3;199-210, 2003   DOI   ScienceOn
30 Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY: A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol 6;1142-1151, 2005   DOI   ScienceOn
31 Akbar AN, Taams LS, Salmon M, Vukmanovic-Stejic M: The peripheral generation of CD4+ CD25+ regulatory T cells. Immunology 109;319-325, 2003   DOI
32 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 162;5317-5326, 1999   PUBMED
33 Youssef AR, Shen CR, Lin CL, Barker RN, Elson CJ: IL-4 and IL-10 modulate autoimmune haemolytic anaemia in NZB mice. Clin Exp Immunol 139;84-89, 2005   DOI   ScienceOn
34 Akbari O, Stock P, DeKruyff RH, Umetsu DT: Role of regulatory T cells in allergy and asthma. Curr Opin Immunol 15;627-633, 2003   DOI   ScienceOn
35 Skapenko A, Kalden JR, Lipsky PE, Schulze-Koops H: The IL-4 receptor alpha-chain-binding cytokines, IL-4 and IL-13, induce forkhead box P3-expressing CD25+CD4+ regulatory T cells from CD25-CD4+ precursors. J Immunol 175;6107-6116, 2005   DOI
36 Vukmanovic-Stejic M, Zhang Y, Cook JE, Fletcher JM, McQuaid A, Masters JE, Rustin MH, Taams LS, Beverley PC, Macallan DC, Akbar AN: Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo. J Clin Invest 116;2423-2433, 2006   DOI   ScienceOn
37 Sakaguchi S: Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22;531-562, 2004   DOI   ScienceOn
38 Wang Z, Hong J, Sun W, Xu G, Li N, Chen X, Liu A, Xu L, Sun B, Zhang JZ: Role of IFN-{gamma} in induction of Foxp3 and conversion of CD4+ CD25- T cells to CD4+ Tregs. J Clin Invest 116;2434-2441, 2006
39 Webb S, Morris C, Sprent J: Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell 63;1249-1256, 1990   DOI   ScienceOn
40 Asano M, Toda M, Sakaguchi N, Sakaguchi S: Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J Exp Med 184;387-396, 1996   DOI
41 Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY: Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22;329- 341, 2005   DOI   ScienceOn
42 Lohr J, Knoechel B, Abbas AK: Regulatory T cells in the periphery. Immunol Rev 212;149-162, 2006   DOI   ScienceOn
43 Apostolou I, von Boehmer H: In vivo instruction of suppressor commitment in naive T cells. J Exp Med 199;1401-1408, 2004   DOI   ScienceOn
44 Zheng SG, Wang JH, Stohl W, Kim KS, Gray JD, Horwitz DA: TGF-beta requires CTLA-4 early after T cell activation to induce FoxP3 and generate adaptive CD4+CD25+ regulatory cells. J Immunol 176;3321-3329, 2006   DOI   PUBMED
45 Liu VC, Wong LY, Jang T, Shah AH, Park I, Yang X, Zhang Q, Lonning S, Teicher BA, Lee C: Tumor evasion of the immune system by converting CD4+CD25- T cells into CD4+CD25+ T regulatory cells: role of tumor-derived TGF-beta. J Immunol 178;2883-2892, 2007   DOI
46 Fehervari Z, Yamaguchi T, Sakaguchi S: The dichotomous role of IL-2: tolerance versus immunity. Trends Immunol 27;109-111, 2006   DOI   ScienceOn
47 Walker MR, Kasprowicz DJ, Gersuk VH, Benard A, Van Landeghen M, Buckner JH, Ziegler SF: Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin Invest 112;1437-1443, 2003   DOI
48 Jones LA, Chin LT, Longo DL, Kruisbeek AM: Peripheral clonal elimination of functional T cells. Science 250;1726-1729, 1990   DOI
49 Zou W: Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6;295-307, 2006   DOI   ScienceOn
50 Valzasina B, Piconese S, Guiducci C, Colombo MP: Tumorinduced expansion of regulatory T cells by conversion of CD4+ CD25- lymphocytes is thymus and proliferation independent. Cancer Res 66;4488-4495, 2006   DOI   ScienceOn
51 Laurie KL, Van Driel IR, Gleeson PA: The role of CD4+ CD25+ immunoregulatory T cells in the induction of autoimmune gastritis. Immunol Cell Biol 80;567-573, 2002   DOI   ScienceOn
52 Zelenay S, Lopes-Carvalho T, Caramalho I, Moraes-Fontes MF, Rebelo M, Demengeot J: Foxp3+ CD25- CD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansion. Proc Natl Acad Sci USA 102;4091-4096, 2005
53 Jonuleit H, Schmitt E, Kakirman H, Stassen M, Knop J, Enk AH: Infectious tolerance: human CD25+ regulatory T cells convey suppressor activity to conventional CD4+ T helper cells. J Exp Med 196;255-260, 2002   DOI   ScienceOn
54 Nishizuka Y, Sakakura T: Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 166;753-755, 1969   DOI   ScienceOn
55 Chen Y, Kuchroo VK, Inobe J, Hafler DA, Weiner HL: Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 265; 1237-1240, 1994   DOI
56 Cosmi L, Liotta F, Lazzeri E, Francalanci M, Angeli R, Mazzinghi B, Santarlasci V, Manetti R, Vanini V, Romagnani P, Maggi E, Romagnani S, Annunziato F: Human CD8+ CD25+ thymocytes share phenotypic and functional features with CD4+ CD25+ regulatory thymocytes. Blood 102; 4107-4114, 2003   DOI   ScienceOn
57 Bluestone JA, Abbas AK: Natural versus adaptive regulatory T cells. Nat Rev Immunol 3;253-257, 2003   DOI   ScienceOn
58 Zheng SG, Wang JH, Gray JD, Soucier H, Horwitz DA: Natural and induced CD4+CD25+ cells educate CD4+CD25- cells to develop suppressive activity: the role of IL-2, TGF-beta, and IL-10. J Immunol 172;5213-5221, 2004   DOI
59 Wang J, Ioan-Facsinay A, van der Voort EI, Huizinga TW, Toes RE: Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur J Immunol 37; 129-138, 2007   DOI   ScienceOn
60 Young DA, Lowe LD, Booth SS, Whitters MJ, Nicholson L, Kuchroo VK, Collins M: IL-4, IL-10, IL-13, and TGF-beta from an altered peptide ligand-specific Th2 cell clone down-regulate adoptive transfer of experimental autoimmune encephalomyelitis. J Immunol 164;3563-3572, 2000   DOI
61 Liston A, Rudensky AY: Thymic development and peripheral homeostasis of regulatory T cells. Curr Opin Immunol 19;176-185, 2007   DOI   ScienceOn
62 Ferber IA, Brocke S, Taylor-Edwards C, Ridgway W, Dinisco C, Steinman L, Dalton D, Fathman CG: Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol 156;5-7, 1996   PUBMED
63 Krakowski M, Owens T: Interferon-gamma confers resistance to experimental allergic encephalomyelitis. Eur J Immunol 26;1641-1646, 1996   DOI   ScienceOn
64 Wan YY, Flavell RA: Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter. Proc Natl Acad Sci USA 102;5126-5131, 2005
65 Thorstenson KM, Khoruts A: Generation of anergic and potentially immunoregulatory CD25+ CD4 T cells in vivo after induction of peripheral tolerance with intravenous or oral antigen. J Immunol 167;188-195, 2001   DOI   PUBMED
66 Zhou G, Levitsky HI: Natural regulatory T cells and de novo-induced regulatory T cells contribute independently to tumor-specific tolerance. J Immunol 178;2155-2162, 2007   DOI
67 Zorn E, Nelson EA, Mohseni M, Porcheray F, Kim H, Litsa D, Bellucci R, Raderschall E, Canning C, Soiffer RJ, Frank DA, Ritz J: IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood 108;1571-1579, 2006   DOI   ScienceOn
68 Kappler JW, Roehm N, Marrack P: T cell tolerance by clonal elimination in the thymus. Cell 49;273-280, 1987   DOI   ScienceOn
69 Surh CD, Sprent J, Webb SR: Exclusion of circulating T cells from the thymus does not apply in the neonatal period. J Exp Med 177;379-385, 1993   DOI
70 Oliveira V, Agua-Doce A, Duarte J, Soares MP, Graca L: Regulatory T cell maintenance of dominant tolerance: induction of tissue self-defense? Transpl Immunol 17;7-10, 2006   DOI   ScienceOn
71 Pacholczyk R, Ignatowicz H, Kraj P, Ignatowicz L: Origin and T cell receptor diversity of Foxp3^+ CD4+ CD25+ T cells. Immunity 25;249-259, 2006   DOI   ScienceOn
72 Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM: Conversion of peripheral CD4+ CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198;1875-1886, 2003   DOI   ScienceOn
73 Fantini MC, Becker C, Monteleone G, Pallone F, Galle PR, Neurath MF: Cutting edge: TGF-{beta} induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7. J Immunol 172;5149-5153, 2004   DOI
74 Davidson TS, Dipaolo RJ, Andersson J, Shevach EM: Cutting edge: IL-2 is essential for TGF-beta-mediated induction of Foxp3+ T regulatory cells. J Immunol 178;4022-4026, 2007   DOI
75 Baecher-Allan C, Hafler DA: Human regulatory T cells and their role in autoimmune disease. Immunol Rev 212;203-216, 2006   DOI   ScienceOn
76 Lechler R, Chai JG, Marelli-Berg F, Lombardi G: The contributions of T-cell anergy to peripheral T-cell tolerance. Immunology 103;262-269, 2001   DOI
77 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 389;737-742, 1997   DOI   ScienceOn
78 Piccirillo CA, Thornton AM: Cornerstone of peripheral tolerance: naturally occurring CD4+ CD25+ regulatory T cells. Trends Immunol 25;374-380, 2004   DOI   ScienceOn
79 Shevach EM: CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol 2;389-400, 2002   DOI   PUBMED
80 Karim M, Kingsley CI, Bushell AR, Sawitzki BS, Wood KJ: Alloantigen-induced CD25+ CD4+ regulatory T cells can develop in vivo from CD25- CD4+ precursors in a thymus-independent process. J Immunol 172;923-928, 2004   DOI   PUBMED