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Article: Efficient generation of human alloantigen-specific CD4 + regulatory T cells from naive precursors by CD40-activated B cells

TitleEfficient generation of human alloantigen-specific CD4 + regulatory T cells from naive precursors by CD40-activated B cells
Authors
Issue Date2008
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
Citation
Blood, 2008, v. 112 n. 6, p. 2554-2562 How to Cite?
AbstractCD4 +CD25 +Foxp3 + regulatory T cells (Treg) play an important role in the induction and maintenance of immune tolerance. Although adoptive transfer of bulk populations of Treg can prevent or treat T cell-mediated inflammatory diseases and transplant allograft rejection in animal models, optimal Treg immunotherapy in humans would ideally use antigen-specific rather than polyclonal Treg for greater specificity of regulation and avoidance of general suppression. However, no robust approaches have been reported for the generation of human antigen-specific Treg at a practical scale for clinical use. Here, we report a simple and cost-effective novel method to rapidly induce and expand large numbers of functional human alloantigenspecific Treg from antigenically naive precursors in vitro using allogeneic nontransformed B cells as stimulators. By this approach naive CD4 +CD25 - T cells could be expanded 8-fold into alloantigenspecific Treg after 3 weeks of culture without any exogenous cytokines. The induced alloantigen-specific Treg were CD45RO +CCR7 - memory cells, and had a CD4 high, CD25 +, Foxp3 +, and CD62L (L-selectin) + phenotype. Although these CD4 hiughCD25 + Foxp3 + alloantigen-specific Treg had no cytotoxic capacity, their suppressive function was cell-cell contact dependent and partially relied on cytotoxic T lymphocyte antigen-4 expression. This approach may accelerate the clinical application of Treg-based immunotherapy in transplantation and autoimmune diseases. © 2008 by The American Society of Hematology.
Persistent Identifierhttp://hdl.handle.net/10722/59530
ISSN
2015 Impact Factor: 11.841
2015 SCImago Journal Rankings: 6.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Seed Funding for Basic Research
University Research Committee
University of Hong Kong (HKU), Hong Kong SAR, PR China
Competitive Earmarked Research Grant
Research Grants Council of Hong Kong, Hong Kong SAR, PR ChinaHKU 777407M
Research Fund for the Control of Infectious Diseases, Hong Kong SAR, PR China07060482
HKU postgraduate studentships
National Institutes of HealthP01 AI-050153
Funding Information:

The authors thank Dr Yan Chen for technical help.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorTu, Wen_HK
dc.contributor.authorLau, YLen_HK
dc.contributor.authorZheng, Jen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorChan, PLen_HK
dc.contributor.authorMao, Hen_HK
dc.contributor.authorDionis, Ken_HK
dc.contributor.authorSchneider, Pen_HK
dc.contributor.authorLewis, DBen_HK
dc.date.accessioned2010-05-31T03:52:05Z-
dc.date.available2010-05-31T03:52:05Z-
dc.date.issued2008en_HK
dc.identifier.citationBlood, 2008, v. 112 n. 6, p. 2554-2562en_HK
dc.identifier.issn0006-4971en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59530-
dc.description.abstractCD4 +CD25 +Foxp3 + regulatory T cells (Treg) play an important role in the induction and maintenance of immune tolerance. Although adoptive transfer of bulk populations of Treg can prevent or treat T cell-mediated inflammatory diseases and transplant allograft rejection in animal models, optimal Treg immunotherapy in humans would ideally use antigen-specific rather than polyclonal Treg for greater specificity of regulation and avoidance of general suppression. However, no robust approaches have been reported for the generation of human antigen-specific Treg at a practical scale for clinical use. Here, we report a simple and cost-effective novel method to rapidly induce and expand large numbers of functional human alloantigenspecific Treg from antigenically naive precursors in vitro using allogeneic nontransformed B cells as stimulators. By this approach naive CD4 +CD25 - T cells could be expanded 8-fold into alloantigenspecific Treg after 3 weeks of culture without any exogenous cytokines. The induced alloantigen-specific Treg were CD45RO +CCR7 - memory cells, and had a CD4 high, CD25 +, Foxp3 +, and CD62L (L-selectin) + phenotype. Although these CD4 hiughCD25 + Foxp3 + alloantigen-specific Treg had no cytotoxic capacity, their suppressive function was cell-cell contact dependent and partially relied on cytotoxic T lymphocyte antigen-4 expression. This approach may accelerate the clinical application of Treg-based immunotherapy in transplantation and autoimmune diseases. © 2008 by The American Society of Hematology.en_HK
dc.languageengen_HK
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/en_HK
dc.relation.ispartofBlooden_HK
dc.subject.meshAntigen Presentation-
dc.subject.meshB-Lymphocytes - cytology - immunology-
dc.subject.meshIsoantigens - immunology-
dc.subject.meshT-Cell Antigen Receptor Specificity-
dc.subject.meshT-Lymphocytes, Regulatory - cytology - immunology-
dc.titleEfficient generation of human alloantigen-specific CD4 + regulatory T cells from naive precursors by CD40-activated B cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-4971&volume=112&issue=6&spage=2554&epage=2562&date=2008&atitle=Efficient+generation+of+human+alloantigen-specific+CD4++regulatory+T+cells+from+naive+precursors+by+CD40-activated+B+cellsen_HK
dc.identifier.emailTu, W:wwtu@hkucc.hku.hken_HK
dc.identifier.emailLau, YL:lauylung@hkucc.hku.hken_HK
dc.identifier.emailLiu, Y:yinpingl@hku.hken_HK
dc.identifier.emailMao, H:hwmau@hku.hken_HK
dc.identifier.authorityTu, W=rp00416en_HK
dc.identifier.authorityLau, YL=rp00361en_HK
dc.identifier.authorityLiu, Y=rp00269en_HK
dc.identifier.authorityMao, H=rp01595en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1182/blood-2008-04-152041en_HK
dc.identifier.pmid18599794-
dc.identifier.pmcidPMC2532818-
dc.identifier.scopuseid_2-s2.0-55249113014en_HK
dc.identifier.hkuros179376en_HK
dc.identifier.hkuros163401-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-55249113014&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume112en_HK
dc.identifier.issue6en_HK
dc.identifier.spage2554en_HK
dc.identifier.epage2562en_HK
dc.identifier.eissn1528-0020-
dc.identifier.isiWOS:000259088000052-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectHumanized mouse as a model to study the antiviral activity of human gammadelta-T cells against human and avian influenza A viruses in vivo-
dc.relation.projectImmune defense of human gammadelta-T cells against Influenza a viruses-
dc.identifier.scopusauthoridTu, W=7006479236en_HK
dc.identifier.scopusauthoridLau, YL=7201403380en_HK
dc.identifier.scopusauthoridZheng, J=55217878700en_HK
dc.identifier.scopusauthoridLiu, Y=35240639600en_HK
dc.identifier.scopusauthoridChan, PL=25631876900en_HK
dc.identifier.scopusauthoridMao, H=25632489000en_HK
dc.identifier.scopusauthoridDionis, K=14123041200en_HK
dc.identifier.scopusauthoridSchneider, P=7402107268en_HK
dc.identifier.scopusauthoridLewis, DB=7404750928en_HK
dc.identifier.citeulike3275180-

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