{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T21:11:49Z","timestamp":1768079509318,"version":"3.49.0"},"reference-count":42,"publisher":"Walter de Gruyter GmbH","issue":"3","license":[{"start":{"date-parts":[[2009,5,29]],"date-time":"2009-05-29T00:00:00Z","timestamp":1243555200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arch. Immunol. Ther. Exp."],"published-print":{"date-parts":[[2009,6]]},"DOI":"10.1007\/s00005-009-0021-1","type":"journal-article","created":{"date-parts":[[2009,5,28]],"date-time":"2009-05-28T09:01:08Z","timestamp":1243501268000},"page":"199-204","source":"Crossref","is-referenced-by-count":26,"title":["Expanding and converting regulatory T cells: a horizon for immunotherapy"],"prefix":"10.2478","volume":"57","author":[{"given":"Mithun","family":"Khattar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanislaw M.","family":"Stepkowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2009,5,29]]},"reference":[{"key":"21_CR1","doi-asserted-by":"crossref","first-page":"8060","DOI":"10.4049\/jimmunol.175.12.8060","volume":"175","author":"CK Asiedu","year":"2005","unstructured":"Asiedu CK, Goodwin KJ, Balgansuren G et\u00a0al (2005) Elevated T regulatory cells in long-term stable transplant tolerance in rhesus macaques induced by anti-CD3 immunotoxin and deoxyspergualin. J Immunol 175: 8060\u20138068","journal-title":"J Immunol"},{"key":"21_CR2","doi-asserted-by":"crossref","first-page":"8338","DOI":"10.4049\/jimmunol.177.12.8338","volume":"177","author":"M Battaglia","year":"2006","unstructured":"Battaglia M, Stabilini A, Migliavacca B et\u00a0al (2006) Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol 177: 8338\u20138347","journal-title":"J Immunol"},{"key":"21_CR3","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nri1032","volume":"3","author":"JA Bluestone","year":"2003","unstructured":"Bluestone JA, Abbas AK (2003) Natural versus adaptive regulatory T cells. Nat Rev Immunol 3: 253\u2013257","journal-title":"Nat Rev Immunol"},{"key":"21_CR4","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1002\/eji.200737791","volume":"38","author":"S Brandenburg","year":"2008","unstructured":"Brandenburg S, Takahashi T, de la RM et\u00a0al (2008) IL-2 induces in vivo suppression by CD4(+)CD25(+)Foxp3(+) regulatory T cells. Eur J Immunol 38: 1643\u20131653","journal-title":"Eur J Immunol"},{"key":"21_CR5","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1084\/jem.20030152","volume":"198","author":"W Chen","year":"2003","unstructured":"Chen W, Jin W, Hardegen N et\u00a0al (2003) Conversion of peripheral CD4+CD25\u2013 naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198: 1875\u20131886","journal-title":"J Exp Med"},{"key":"21_CR6","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1084\/jem.20070590","volume":"204","author":"JL Coombes","year":"2007","unstructured":"Coombes JL, Siddiqui KR, rancibia-Carcamo CV et\u00a0al (2007) 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 204: 1757\u20131764","journal-title":"J Exp Med"},{"key":"21_CR7","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1002\/eji.200738104","volume":"38","author":"CM Costantino","year":"2008","unstructured":"Costantino CM, Baecher-Allan CM, Hafler DA (2008) Human regulatory T cells and autoimmunity. Eur J Immunol 38: 921\u2013924","journal-title":"Eur J Immunol"},{"key":"21_CR8","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.4049\/jimmunol.178.7.4136","volume":"178","author":"KN Couper","year":"2007","unstructured":"Couper KN, Blount DG, de Souza JB et\u00a0al (2007) Incomplete depletion and rapid regeneration of Foxp3+ regulatory T cells following anti-CD25 treatment in malaria-infected mice. J Immunol 178: 4136\u20134146","journal-title":"J Immunol"},{"key":"21_CR9","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1097\/TP.0b013e318166910b","volume":"85","author":"A Demirkiran","year":"2008","unstructured":"Demirkiran A, Hendrikx TK, Baan CC et\u00a0al (2008) Impact of immunosuppressive drugs on CD4+CD25+FOXP3+ regulatory T cells: does in vitro evidence translate to the clinical setting. Transplantation 85: 783\u2013789","journal-title":"Transplantation"},{"key":"21_CR10","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1136\/gut.2005.072801","volume":"55","author":"MC Fantini","year":"2006","unstructured":"Fantini MC, Becker C, Tubbe I et\u00a0al (2006) Transforming growth factor beta induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis. Gut 55: 671\u2013680","journal-title":"Gut"},{"key":"21_CR11","doi-asserted-by":"crossref","first-page":"15770","DOI":"10.1073\/pnas.232583599","volume":"99","author":"S Fiorucci","year":"2002","unstructured":"Fiorucci S, Antonelli E, Distrutti E et\u00a0al (2002) NCX-1015, a nitric-oxide derivative of prednisolone, enhances regulatory T cells in the lamina propria and protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis in mice. Proc Natl Acad Sci USA 99: 15770\u201315775","journal-title":"Proc Natl Acad Sci USA"},{"key":"21_CR12","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.immuni.2005.01.016","volume":"22","author":"JD Fontenot","year":"2005","unstructured":"Fontenot JD, Rasmussen JP, Williams LM et\u00a0al (2005) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22: 329\u2013341","journal-title":"Immunity"},{"key":"21_CR13","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1111\/j.1600-6143.2007.01842.x","volume":"7","author":"W Gao","year":"2007","unstructured":"Gao W, Lu Y, El EB et al (2007) Contrasting effects of cyclosporine and rapamycin in de novo generation of alloantigen-specific regulatory T cells. Am J Transplant 7: 1722\u20131732","journal-title":"Am J Transplant"},{"key":"21_CR14","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1182\/blood-2006-05-025460","volume":"109","author":"D Golshayan","year":"2007","unstructured":"Golshayan D, Jiang S, Tsang J et al (2007) In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance. Blood 109: 827\u2013835","journal-title":"Blood"},{"key":"21_CR15","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00005-008-0015-4","volume":"56","author":"S Gupta","year":"2008","unstructured":"Gupta S, Shang W, Sun Z (2008) Mechanisms regulating the development and function of natural regulatory T cells. Arch Immunol Ther Exp 56: 85\u2013102","journal-title":"Arch Immunol Ther Exp"},{"key":"21_CR16","doi-asserted-by":"crossref","first-page":"8344","DOI":"10.1158\/0008-5472.CAN-06-3304","volume":"67","author":"S Hinz","year":"2007","unstructured":"Hinz S, Pagerols-Raluy L, Oberg HH et al (2007) Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer. Cancer Res 67: 8344\u20138350","journal-title":"Cancer Res"},{"key":"21_CR17","doi-asserted-by":"crossref","first-page":"6449","DOI":"10.1073\/pnas.0502187102","volume":"102","author":"J Hong","year":"2005","unstructured":"Hong J, Li N, Zhang X et al (2005) Induction of CD4+CD25+ regulatory T cells by copolymer-I through activation of transcription factor Foxp3. Proc Natl Acad Sci USA 102: 6449\u20136454","journal-title":"Proc Natl Acad Sci USA"},{"key":"21_CR18","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1002\/eji.200738109","volume":"38","author":"DA Horwitz","year":"2008","unstructured":"Horwitz DA, Zheng SG, Wang J et al (2008) Critical role of IL-2 and TGF-beta in generation, function and stabilization of Foxp3+CD4+ Treg. Eur J Immunol 38: 912\u2013915","journal-title":"Eur J Immunol"},{"key":"21_CR19","doi-asserted-by":"crossref","first-page":"7849","DOI":"10.4049\/jimmunol.178.12.7849","volume":"178","author":"HK Kang","year":"2007","unstructured":"Kang HK, Liu M, Datta SK (2007) 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 178: 7849\u20137858","journal-title":"J Immunol"},{"key":"21_CR20","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1600-6143.2006.01604.x","volume":"7","author":"E Kreijveld","year":"2007","unstructured":"Kreijveld E, Koenen HJ, Klasen IS et al (2007) Following anti-CD25 treatment, a functional CD4+CD25+ regulatory T-cell pool is present in renal transplant recipients. Am J Transplant 7: 249\u2013255","journal-title":"Am J Transplant"},{"key":"21_CR21","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/ni1265","volume":"6","author":"K Kretschmer","year":"2005","unstructured":"Kretschmer K, Apostolou I, Hawiger D et al (2005) Inducing and expanding regulatory T cell populations by foreign antigen. Nat Immunol 6: 1219\u20131227","journal-title":"Nat Immunol"},{"key":"21_CR22","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1084\/jem.20041201","volume":"201","author":"S Liang","year":"2005","unstructured":"Liang S, Alard P, Zhao Y et al (2005) Conversion of CD4+ CD25\u2013 cells into CD4+ CD25+ regulatory T cells in vivo requires B7 costimulation, but not the thymus. J Exp Med 201: 127\u2013137","journal-title":"J Exp Med"},{"key":"21_CR23","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.immuni.2007.11.021","volume":"28","author":"CW Lio","year":"2008","unstructured":"Lio CW, Hsieh CS (2008) A two-step process for thymic regulatory T cell development. Immunity 28: 100\u2013111","journal-title":"Immunity"},{"key":"21_CR24","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.coi.2007.02.005","volume":"19","author":"A Liston","year":"2007","unstructured":"Liston A, Rudensky AY (2007) Thymic development and peripheral homeostasis of regulatory T cells. Curr Opin Immunol 19: 176\u2013185","journal-title":"Curr Opin Immunol"},{"key":"21_CR25","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1073\/pnas.0611646104","volume":"104","author":"X Luo","year":"2007","unstructured":"Luo X, Tarbell KV, Yang H et al (2007) Dendritic cells with TGF-beta1 differentiate naive CD4+CD25\u2013 T cells into isletprotective Foxp3+ regulatory T cells. Proc Natl Acad Sci USA 104: 2821\u20132826","journal-title":"Proc Natl Acad Sci USA"},{"key":"21_CR26","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.4049\/jimmunol.179.4.2170","volume":"179","author":"Y Matsumura","year":"2007","unstructured":"Matsumura Y, Kobayashi T, Ichiyama K et al (2007) Selective expansion of foxp3-positive regulatory T cells and immunosuppression by suppressors of cytokine signaling 3-deficient dendritic cells. J Immunol 179: 2170\u20132179","journal-title":"J Immunol"},{"key":"21_CR27","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1126\/science.1145697","volume":"317","author":"D Mucida","year":"2007","unstructured":"Mucida D, Park Y, Kim G et al (2007) Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317: 256\u2013260","journal-title":"Science"},{"key":"21_CR28","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nature06051","volume":"444","author":"DJ Pennington","year":"2006","unstructured":"Pennington DJ, Silva-Santos B, Silberzahn T et al (2006) Early events in the thymus affect the balance of effector and regulatory T cells. Nature 444: 1073\u20131077","journal-title":"Nature"},{"key":"21_CR29","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.immunol.21.120601.141122","volume":"22","author":"S Sakaguchi","year":"2004","unstructured":"Sakaguchi S (2004) Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22: 531\u2013562","journal-title":"Annu Rev Immunol"},{"key":"21_CR30","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S1074-7613(00)80195-8","volume":"12","author":"B Salomon","year":"2000","unstructured":"Salomon B, Lenschow DJ, Rhee L et al (2000) B7\/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12: 431\u2013440","journal-title":"Immunity"},{"key":"21_CR31","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1084\/jem.20062105","volume":"204","author":"JP Scott-Browne","year":"2007","unstructured":"Scott-Browne JP, Shafiani S, Tucker-Heard G et al (2007) Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis. J Exp Med 204: 2159\u20132169","journal-title":"J Exp Med"},{"key":"21_CR32","doi-asserted-by":"crossref","first-page":"7667","DOI":"10.4049\/jimmunol.178.12.7667","volume":"178","author":"RK Selvaraj","year":"2007","unstructured":"Selvaraj RK, Geiger TL (2007) A kinetic and dynamic analysis of Foxp3 induced in T cells by TGF-beta. J Immunol 178: 7667\u20137677","journal-title":"J Immunol"},{"key":"21_CR33","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1084\/jem.20040139","volume":"199","author":"Q Tang","year":"2004","unstructured":"Tang Q, Henriksen KJ, Bi M et al (2004) In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J Exp Med 199: 1455\u20131465","journal-title":"J Exp Med"},{"key":"21_CR34","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1038\/nm1652","volume":"13","author":"R Tao","year":"2007","unstructured":"Tao R, de Zoeten EF, Ozkaynak E et al (2007) Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat Med 13: 1299\u20131307","journal-title":"Nat Med"},{"key":"21_CR35","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1084\/jem.20040180","volume":"199","author":"KV Tarbell","year":"2004","unstructured":"Tarbell KV, Yamazaki S, Olson K et al (2004) CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J Exp Med 199: 1467\u20131477","journal-title":"J Exp Med"},{"key":"21_CR36","doi-asserted-by":"crossref","first-page":"3651","DOI":"10.4049\/jimmunol.180.6.3651","volume":"180","author":"H Tuovinen","year":"2008","unstructured":"Tuovinen H, Kekalainen E, Rossi LH et al (2008) Cutting edge: human CD4\u2013CD8\u2013 thymocytes express FOXP3 in the absence of a TCR. J Immunol 180: 3651\u20133654","journal-title":"J Immunol"},{"key":"21_CR37","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.2741\/2773","volume":"13","author":"LA Turka","year":"2008","unstructured":"Turka LA, Walsh PT (2008) IL-2 signaling and CD4+ CD25+ Foxp3+ regulatory T cells. Front Biosci 13: 1440\u20131446","journal-title":"Front Biosci"},{"key":"21_CR38","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1513\/pats.200701-020AW","volume":"4","author":"YY Wan","year":"2007","unstructured":"Wan YY, Flavell RA (2007) Regulatory T cells, transforming growth factor-beta, and immune suppression. Proc Am Thorac Soc 4: 271\u2013276","journal-title":"Proc Am Thorac Soc"},{"key":"21_CR39","first-page":"2434","volume":"116","author":"Z Wang","year":"2006","unstructured":"Wang Z, Hong J, Sun W et al (2006) Role of IFN-gamma in induction of Foxp3 and conversion of CD4+CD25\u2013 T cells to CD4+ Tregs. J Clin Invest 116: 2434\u20132441","journal-title":"J Clin Invest"},{"key":"21_CR40","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1126\/science.1160062","volume":"322","author":"K Wing","year":"2008","unstructured":"Wing K, Onishi Y, Prieto-Martin P et al (2008) CTLA-4 control over Foxp3+ regulatory T cell function. Science 322: 271\u2013275","journal-title":"Science"},{"key":"21_CR41","doi-asserted-by":"crossref","first-page":"5213","DOI":"10.4049\/jimmunol.172.9.5213","volume":"172","author":"SG Zheng","year":"2004","unstructured":"Zheng SG, Wang JH, Gray JD et al (2004) Natural and induced CD4+CD25+ cells educate CD4+CD25\u2013 cells to develop suppressive activity: the role of IL-2, TGF-beta, and IL-10. J Immunol 172: 5213\u20135221","journal-title":"J Immunol"},{"key":"21_CR42","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.4049\/jimmunol.178.4.2018","volume":"178","author":"SG Zheng","year":"2007","unstructured":"Zheng SG, Wang J, Wang P et al (2007) IL-2 is essential for TGF-beta to convert naive CD4+CD25\u2013 cells to CD25+Foxp3+ regulatory T cells and for expansion of these cells. J Immunol 178: 2018\u20132027","journal-title":"J Immunol"}],"container-title":["Archivum Immunologiae et Therapiae Experimentalis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00005-009-0021-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00005-009-0021-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00005-009-0021-1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T20:46:48Z","timestamp":1704228408000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00005-009-0021-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,5,29]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,6]]}},"alternative-id":["21"],"URL":"https:\/\/doi.org\/10.1007\/s00005-009-0021-1","relation":{},"ISSN":["0004-069X","1661-4917"],"issn-type":[{"value":"0004-069X","type":"print"},{"value":"1661-4917","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,5,29]]}}}