{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:15:41Z","timestamp":1792790141487,"version":"4.5.0"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2009,12,27]],"date-time":"2009-12-27T00:00:00Z","timestamp":1261872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI067541"],"award-info":[{"award-number":["R01 AI067541"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI060994"],"award-info":[{"award-number":["R01 AI060994"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50-GM-53789"],"award-info":[{"award-number":["P50-GM-53789"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R33-HL-089082"],"award-info":[{"award-number":["R33-HL-089082"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health Institutional","award":["T32 AI74490"],"award-info":[{"award-number":["T32 AI74490"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Minimization of immunosuppression and donor-specific tolerance to MHC-mismatched organ grafts are important clinical goals. The therapeutic potential of regulatory T cells (Tregs) has been demonstrated, but conditions for optimizing their in vivo function posttransplant in nonlymphocyte-depleted hosts remain undefined. In this study, we address mechanisms through which inhibition of the mammalian target of rapamycin (Rapa) synergizes with alloantigen-specific Treg (AAsTreg) to permit long-term, donor-specific heart graft survival in immunocompetent hosts. Crucially, immature allogeneic dendritic cells allowed AAsTreg selection in vitro, with minimal expansion of unwanted (Th17) cells. The rendered Treg potently inhibited T cell proliferation in an Ag-specific manner. However, these AAsTreg remained unable to control T cells stimulated by allogeneic mature dendritic cells, a phenomenon dependent on the release of proinflammatory cytokines. In vivo, Rapa administration reduced danger-associated IL-6 production, T cell proliferation, and graft infiltration. Based on these observations, AAsTreg were administered posttransplant (day 7) in combination with a short course of Rapa and rendered &amp;gt;80% long-term (&amp;gt;150 d) graft survival, a result superior to that achieved with polyclonal Treg. Moreover, graft protection was alloantigen-specific. Significantly, long-term graft survival was associated with alloreactive T cell anergy. These findings delineate combination of transient mammalian target of Rapa inhibition with appropriate AAsTreg selection as an effective approach to promote long-term organ graft survival.<\/jats:p>","DOI":"10.4049\/jimmunol.0900936","type":"journal-article","created":{"date-parts":[[2009,12,9]],"date-time":"2009-12-09T22:26:22Z","timestamp":1260397582000},"page":"624-636","source":"Crossref","is-referenced-by-count":92,"title":["Mammalian Target of Rapamycin Inhibition and Alloantigen-Specific Regulatory T Cells Synergize To Promote Long-Term Graft Survival in Immunocompetent Recipients"],"prefix":"10.1093","volume":"184","author":[{"given":"Giorgio","family":"Raimondi","sequence":"first","affiliation":[{"name":"Starzl Transplantation Institute"},{"name":"Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina L","family":"Sumpter","sequence":"additional","affiliation":[{"name":"Starzl Transplantation Institute"},{"name":"Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin M","family":"Matta","sequence":"additional","affiliation":[{"name":"Starzl Transplantation Institute"},{"name":"Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Pillai","sequence":"additional","affiliation":[{"name":"Starzl Transplantation Institute"},{"name":"Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Corbitt","sequence":"additional","affiliation":[{"name":"Starzl Transplantation Institute"},{"name":"Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoram","family":"Vodovotz","sequence":"additional","affiliation":[{"name":"Department of Surgery"},{"name":"Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15213"},{"name":"Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine , Pittsburgh, PA 15219"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Starzl Transplantation Institute"},{"name":"Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus W","family":"Thomson","sequence":"additional","affiliation":[{"name":"Starzl Transplantation Institute"},{"name":"Department of Surgery"},{"name":"Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,27]]},"reference":[{"key":"2026012808084990400_r1","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/nm1251","article-title":"Organ transplantation\u2014how much of the promise has been realized?","volume":"11","author":"Lechler","year":"2005","journal-title":"Nat. Med."},{"key":"2026012808084990400_r2","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/nri2132","article-title":"Tolerogenic dendritic cells and the quest for transplant tolerance.","volume":"7","author":"Morelli","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"2026012808084990400_r3","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1600-065X.2006.00428.x","article-title":"Immune privilege induced by regulatory T cells in transplantation tolerance.","volume":"213","author":"Cobbold","year":"2006","journal-title":"Immunol. Rev."},{"key":"2026012808084990400_r4","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1111\/j.1600-6143.2007.01829.x","article-title":"CD4+CD25+ regulatory T cells in transplantation: progress, challenges and prospects.","volume":"7","author":"Kang","year":"2007","journal-title":"Am. J. Transplant."},{"key":"2026012808084990400_r5","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1097\/MOT.0b013e3283061137","article-title":"Regulatory T cells: hypes and limitations.","volume":"13","author":"Schiopu","year":"2008","journal-title":"Curr. Opin. Organ Transplant."},{"key":"2026012808084990400_r6","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nri2138","article-title":"Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans.","volume":"7","author":"Roncarolo","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"2026012808084990400_r7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1615\/CritRevImmunol.v27.i1.50","article-title":"Naturally occurring regulatory T cells: recent insights in health and disease.","volume":"27","author":"Raimondi","year":"2007","journal-title":"Crit. Rev. Immunol."},{"key":"2026012808084990400_r8","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1097\/00007890-199611150-00002","article-title":"Amplification of natural regulatory immune mechanisms for transplantation tolerance.","volume":"62","author":"Chen","year":"1996","journal-title":"Transplantation"},{"key":"2026012808084990400_r9","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1084\/jem.171.1.141","article-title":"Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. III. Further characterization of the CD4+ suppressor cell and its mechanisms of action.","volume":"171","author":"Hall","year":"1990","journal-title":"J. Exp. Med."},{"key":"2026012808084990400_r10","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nri1027","article-title":"Regulatory T cells in transplantation tolerance.","volume":"3","author":"Wood","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2026012808084990400_r11","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance.","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"key":"2026012808084990400_r12","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/j.0105-2896.2006.00423.x","article-title":"Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation.","volume":"212","author":"Izcue","year":"2006","journal-title":"Immunol. Rev."},{"key":"2026012808084990400_r13","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/ni1572","article-title":"The Foxp3+ regulatory T cell: a jack of all trades, master of regulation.","volume":"9","author":"Tang","year":"2008","journal-title":"Nat. Immunol."},{"key":"2026012808084990400_r14","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1111\/j.1600-6143.2008.02306.x","article-title":"T-regulatory cells in human transplantation.","volume":"8","author":"Racusen","year":"2008","journal-title":"Am. J. Transplant."},{"key":"2026012808084990400_r15","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nri1574","article-title":"Regulatory T-cell therapy: is it ready for the clinic?","volume":"5","author":"Bluestone","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"2026012808084990400_r16","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1182\/blood-2006-05-025460","article-title":"In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance.","volume":"109","author":"Golshayan","year":"2007","journal-title":"Blood"},{"key":"2026012808084990400_r17","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nm1688","article-title":"Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes.","volume":"14","author":"Joffre","year":"2008","journal-title":"Nat. Med."},{"key":"2026012808084990400_r18","doi-asserted-by":"crossref","first-page":"3804","DOI":"10.1182\/blood-2004-05-1850","article-title":"L-Selectin(hi) but not the L-selectin(lo) CD4+25+ T-regulatory cells are potent inhibitors of GVHD and BM graft rejection.","volume":"104","author":"Taylor","year":"2004","journal-title":"Blood"},{"key":"2026012808084990400_r19","doi-asserted-by":"crossref","first-page":"3789","DOI":"10.4049\/jimmunol.166.6.3789","article-title":"IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo.","volume":"166","author":"Hara","year":"2001","journal-title":"J. Immunol."},{"key":"2026012808084990400_r20","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/j.1600-6143.2007.02088.x","article-title":"Ex vivo-expanded natural CD4+CD25+ regulatory T cells synergize with host T-cell depletion to promote long-term survival of allografts.","volume":"8","author":"Xia","year":"2008","journal-title":"Am. J. Transplant."},{"key":"2026012808084990400_r21","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/nri1002","article-title":"The complementary roles of deletion and regulation in transplantation tolerance.","volume":"3","author":"Lechler","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2026012808084990400_r22","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1126\/science.1078231","article-title":"Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells.","volume":"299","author":"Pasare","year":"2003","journal-title":"Science"},{"key":"2026012808084990400_r23","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/j.1365-2567.2009.03053.x","article-title":"Regulatory T cells overturned: the effectors fight back.","volume":"126","author":"Walker","year":"2009","journal-title":"Immunology"},{"key":"2026012808084990400_r24","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1097\/MOT.0b013e3283061149","article-title":"Toll-like receptor signaling in transplantation.","volume":"13","author":"Alegre","year":"2008","journal-title":"Curr. Opin. Organ Transplant."},{"key":"2026012808084990400_r25","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1097\/00007890-199811270-00021","article-title":"Combined costimulation blockade plus rapamycin but not cyclosporine produces permanent engraftment.","volume":"66","author":"Li","year":"1998","journal-title":"Transplantation"},{"key":"2026012808084990400_r26","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nri2546","article-title":"Immunoregulatory functions of mTOR inhibition.","volume":"9","author":"Thomson","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"2026012808084990400_r27","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1038\/15260","article-title":"Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance.","volume":"5","author":"Wells","year":"1999","journal-title":"Nat. Med."},{"key":"2026012808084990400_r28","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1182\/blood-2007-06-094482","article-title":"Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells.","volume":"111","author":"Zeiser","year":"2008","journal-title":"Blood"},{"key":"2026012808084990400_r29","doi-asserted-by":"crossref","first-page":"5794","DOI":"10.4049\/jimmunol.180.9.5794","article-title":"Cutting edge: Foxp3-mediated induction of pim 2 allows human T regulatory cells to preferentially expand in rapamycin.","volume":"180","author":"Basu","year":"2008","journal-title":"J. Immunol."},{"key":"2026012808084990400_r30","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1182\/blood-2004-10-3932","article-title":"Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells.","volume":"105","author":"Battaglia","year":"2005","journal-title":"Blood"},{"key":"2026012808084990400_r31","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1111\/j.1600-6143.2007.01842.x","article-title":"Contrasting effects of cyclosporine and rapamycin in de novo generation of alloantigen-specific regulatory T cells.","volume":"7","author":"Gao","year":"2007","journal-title":"Am. J. Transplant."},{"key":"2026012808084990400_r32","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1084\/jem.20060772","article-title":"CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells.","volume":"203","author":"Liu","year":"2006","journal-title":"J. Exp. Med."},{"key":"2026012808084990400_r33","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1084\/jem.20060468","article-title":"Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells.","volume":"203","author":"Seddiki","year":"2006","journal-title":"J. Exp. Med."},{"key":"2026012808084990400_r34","doi-asserted-by":"crossref","first-page":"7018","DOI":"10.4049\/jimmunol.178.11.7018","article-title":"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.","volume":"178","author":"Turnquist","year":"2007","journal-title":"J. Immunol."},{"key":"2026012808084990400_r35","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.4049\/jimmunol.176.5.2808","article-title":"Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ resting regulatory T cells from activated T cells.","volume":"176","author":"Raimondi","year":"2006","journal-title":"J. Immunol."},{"key":"2026012808084990400_r36","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1084\/jem.184.5.1953","article-title":"Dramatic increase in the numbers of functionally mature dendritic cells in Flt3 ligand-treated mice: multiple dendritic cell subpopulations identified.","volume":"184","author":"Maraskovsky","year":"1996","journal-title":"J. Exp. Med."},{"key":"2026012808084990400_r37","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1182\/blood-2002-09-2929","article-title":"Dendritic cell subsets in blood and lymphoid tissue of rhesus monkeys and their mobilization with Flt3 ligand.","volume":"102","author":"Coates","year":"2003","journal-title":"Blood"},{"key":"2026012808084990400_r38","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/j.1600-6143.2004.00673.x","article-title":"Rapamycin-treated, alloantigen-pulsed host dendritic cells induce ag-specific T cell regulation and prolong graft survival.","volume":"5","author":"Taner","year":"2005","journal-title":"Am. J. Transplant."},{"key":"2026012808084990400_r39","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1084\/jem.20081359","article-title":"Antigen-specific peripheral shaping of the natural regulatory T cell population.","volume":"205","author":"Lathrop","year":"2008","journal-title":"J. Exp. Med."},{"key":"2026012808084990400_r40","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.4049\/jimmunol.179.6.3412","article-title":"Cutting edge: size and diversity of CD4+CD25high Foxp3+ regulatory T cell repertoire in humans: evidence for similarities and partial overlapping with CD4+CD25- T cells.","volume":"179","author":"Fazilleau","year":"2007","journal-title":"J. Immunol."},{"key":"2026012808084990400_r41","doi-asserted-by":"crossref","first-page":"7032","DOI":"10.4049\/jimmunol.178.11.7032","article-title":"Adaptation of TCR repertoires to self-peptides in regulatory and nonregulatory CD4+ T cells.","volume":"178","author":"Wong","year":"2007","journal-title":"J. Immunol."},{"key":"2026012808084990400_r42","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.4049\/jimmunol.178.5.2961","article-title":"Regulatory T cells dynamically control the primary immune response to foreign antigen.","volume":"178","author":"Haribhai","year":"2007","journal-title":"J. Immunol."},{"key":"2026012808084990400_r43","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.immuni.2004.07.009","article-title":"Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors.","volume":"21","author":"Hsieh","year":"2004","journal-title":"Immunity"},{"key":"2026012808084990400_r44","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/eji.200636577","article-title":"Activation of CD4+ CD25+ regulatory T cell suppressor function by analogs of the selecting peptide.","volume":"37","author":"Larkin","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"2026012808084990400_r45","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.4049\/jimmunol.176.5.2691","article-title":"Patients, pathogens, and protective immunity: the relevance of virus-induced alloreactivity in transplantation.","volume":"176","author":"Koehn","year":"2006","journal-title":"J. Immunol."},{"key":"2026012808084990400_r46","doi-asserted-by":"crossref","first-page":"2758","DOI":"10.1073\/pnas.0510606103","article-title":"Effective expansion of alloantigen-specific Foxp3+ CD25+ CD4+ regulatory T cells by dendritic cells during the mixed leukocyte reaction.","volume":"103","author":"Yamazaki","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026012808084990400_r47","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1084\/jem.20081937","article-title":"A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy.","volume":"205","author":"Yuan","year":"2008","journal-title":"J. Exp. Med."},{"key":"2026012808084990400_r48","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1038\/nature07036","article-title":"Induction and effector functions of T(H)17 cells.","volume":"453","author":"Bettelli","year":"2008","journal-title":"Nature"},{"key":"2026012808084990400_r49","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/ni1455","article-title":"Foxp3 in control of the regulatory T cell lineage.","volume":"8","author":"Zheng","year":"2007","journal-title":"Nat. Immunol."},{"key":"2026012808084990400_r50","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/ni.1774","article-title":"Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo.","volume":"10","author":"Zhou","year":"2009","journal-title":"Nat. Immunol."},{"key":"2026012808084990400_r51","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1002\/eji.200738109","article-title":"Critical role of IL-2 and TGF-\u03b2 in generation, function and stabilization of Foxp3+CD4+ Treg.","volume":"38","author":"Horwitz","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"2026012808084990400_r52","doi-asserted-by":"crossref","first-page":"6725","DOI":"10.4049\/jimmunol.178.11.6725","article-title":"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-\u03b2.","volume":"178","author":"Xu","year":"2007","journal-title":"J. Immunol."},{"key":"2026012808084990400_r53","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.immuni.2008.12.022","article-title":"Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response.","volume":"30","author":"Zhang","year":"2009","journal-title":"Immunity"},{"key":"2026012808084990400_r54","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1084\/jem.20031562","article-title":"Developmental stage, phenotype, and migration distinguish naive- and effector\/memory-like CD4+ regulatory T cells.","volume":"199","author":"Huehn","year":"2004","journal-title":"J. Exp. Med."},{"key":"2026012808084990400_r55","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.immuni.2004.08.010","article-title":"Role of LAG-3 in regulatory T cells.","volume":"21","author":"Huang","year":"2004","journal-title":"Immunity"},{"key":"2026012808084990400_r56","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1111\/j.1600-6143.2006.01372.x","article-title":"T regulatory cells and migration.","volume":"6","author":"Chen","year":"2006","journal-title":"Am. J. Transplant."},{"key":"2026012808084990400_r57","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.smim.2006.01.004","article-title":"Antigen-specific regulatory T cells\u2014ex vivo expansion and therapeutic potential.","volume":"18","author":"Masteller","year":"2006","journal-title":"Semin. Immunol."},{"key":"2026012808084990400_r58","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/nri821","article-title":"CD4+ CD25+ suppressor T cells: more questions than answers.","volume":"2","author":"Shevach","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"2026012808084990400_r59","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nm1564","article-title":"Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation.","volume":"13","author":"Korn","year":"2007","journal-title":"Nat. Med."},{"key":"2026012808084990400_r60","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1084\/jem.20012097","article-title":"Identification of regulatory T cells in tolerated allografts.","volume":"195","author":"Graca","year":"2002","journal-title":"J. Exp. Med."},{"key":"2026012808084990400_r61","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1016\/S0041-1345(01)01960-1","article-title":"Regulatory tolerance-mediating T cells in transplantation tolerance.","volume":"33","author":"Sawitzki","year":"2001","journal-title":"Transplant. Proc."},{"key":"2026012808084990400_r62","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1146\/annurev.immunol.25.022106.141557","article-title":"IL-17 family cytokines and the expanding diversity of effector T cell lineages.","volume":"25","author":"Weaver","year":"2007","journal-title":"Annu. Rev. Immunol."},{"key":"2026012808084990400_r63","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.immuni.2006.01.001","article-title":"TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells.","volume":"24","author":"Veldhoen","year":"2006","journal-title":"Immunity"},{"key":"2026012808084990400_r64","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.2353\/ajpath.2008.070207","article-title":"Interleukin-13 protects against experimental autoimmune myocarditis by regulating macrophage differentiation.","volume":"172","author":"Cihakova","year":"2008","journal-title":"Am. J. Pathol."},{"key":"2026012808084990400_r65","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.4049\/jimmunol.182.2.1167","article-title":"Galectin-3 deficiency reduces the severity of experimental autoimmune encephalomyelitis.","volume":"182","author":"Jiang","year":"2009","journal-title":"J. Immunol."},{"key":"2026012808084990400_r66","doi-asserted-by":"crossref","first-page":"7117","DOI":"10.4049\/jimmunol.180.11.7117","article-title":"Plasticity of regulatory T cells: subversion of suppressive function and conversion to enhancement of lung allergic responses.","volume":"180","author":"Joetham","year":"2008","journal-title":"J. Immunol."},{"key":"2026012808084990400_r67","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.4049\/jimmunol.180.4.2679","article-title":"IL-13-mediated gender difference in susceptibility to autoimmune encephalomyelitis.","volume":"180","author":"Sinha","year":"2008","journal-title":"J. Immunol."},{"key":"2026012808084990400_r68","doi-asserted-by":"crossref","first-page":"6107","DOI":"10.4049\/jimmunol.175.9.6107","article-title":"The IL-4 receptor \u03b1-chain-binding cytokines, IL-4 and IL-13, induce forkhead box P3-expressing CD25+CD4+ regulatory T cells from CD25-CD4+ precursors.","volume":"175","author":"Skapenko","year":"2005","journal-title":"J. Immunol."},{"key":"2026012808084990400_r69","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/ni1437","article-title":"Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3.","volume":"8","author":"Williams","year":"2007","journal-title":"Nat. Immunol."},{"key":"2026012808084990400_r70","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/ni1445","article-title":"Regulatory T cell development in the absence of functional Foxp3.","volume":"8","author":"Lin","year":"2007","journal-title":"Nat. Immunol."},{"key":"2026012808084990400_r71","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/nature05479","article-title":"Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression.","volume":"445","author":"Wan","year":"2007","journal-title":"Nature"},{"key":"2026012808084990400_r72","doi-asserted-by":"crossref","first-page":"7797","DOI":"10.1073\/pnas.0800928105","article-title":"T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR.","volume":"105","author":"Sauer","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026012808084990400_r73","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.immuni.2004.10.006","article-title":"Toll-dependent control mechanisms of CD4 T cell activation.","volume":"21","author":"Pasare","year":"2004","journal-title":"Immunity"},{"key":"2026012808084990400_r74","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.4049\/jimmunol.176.7.4021","article-title":"Induction of peripheral T cell tolerance by antigen-presenting B cells. II. Chronic antigen presentation overrules antigen-presenting B cell activation.","volume":"176","author":"Raimondi","year":"2006","journal-title":"J. Immunol."},{"key":"2026012808084990400_r75","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.4049\/jimmunol.176.7.4012","article-title":"Induction of peripheral T cell tolerance by antigen-presenting B cells. I. Relevance of antigen presentation persistence.","volume":"176","author":"Raimondi","year":"2006","journal-title":"J. Immunol."},{"key":"2026012808084990400_r76","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.1172\/JCI33185","article-title":"Conferring indirect allospecificity on CD4+CD25+ Tregs by TCR gene transfer favors transplantation tolerance in mice.","volume":"118","author":"Tsang","year":"2008","journal-title":"J. Clin. Invest."},{"key":"2026012808084990400_r77","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1097\/01.tp.0000244932.29542.9e","article-title":"Generation and expansion of human CD4+ CD25+ regulatory T cells with indirect allospecificity: Potential reagents to promote donor-specific transplantation tolerance.","volume":"82","author":"Jiang","year":"2006","journal-title":"Transplantation"},{"key":"2026012808084990400_r78","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/j.1600-065X.2008.00637.x","article-title":"Human regulatory T cells: role in autoimmune disease and therapeutic opportunities.","volume":"223","author":"Brusko","year":"2008","journal-title":"Immunol. Rev."},{"key":"2026012808084990400_r79","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1182\/blood-2007-06-094656","article-title":"Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-\u03b2 dependent but does not confer a regulatory phenotype.","volume":"110","author":"Tran","year":"2007","journal-title":"Blood"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/2\/624\/62719566\/ji_0900936.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/2\/624\/62719566\/ji_0900936.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T13:09:40Z","timestamp":1769605780000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/184\/2\/624\/8013467"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12,27]]},"references-count":79,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2009,12,27]]},"published-print":{"date-parts":[[2010,1,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0900936","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,1]]},"published":{"date-parts":[[2009,12,27]]}}}