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Article: Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells

TitleEfficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells
Authors
Issue Date2009
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
Citation
Journal Of Immunology, 2009, v. 183 n. 6, p. 3742-3750 How to Cite?
AbstractAlthough recent studies have focused on CD4 + regulatory T cells (Treg), CD8 + Treg have also been reported to play important roles in the induction and maintenance of immune tolerance. Adoptive transfer of CD8 + Treg in rodents or induction of CD8 + Treg in humans can prevent or treat allograft rejection and autoimmune diseases. However, no approaches have been reported for the generation of human Ag-specific CD8 + Treg at a practical scale for clinical use. Here, we found that two novel CD8 + T cell subsets with different levels of CD8 surface expression, CD8 high and CD8 low, could be induced from naive CD8 + precursors in vitro by allogeneic CD40-activated B cells, whereas only CD8 high T cells were alloantigen-specific Treg with relatively poor alloantigen-specific cytotoxicity. Importantly, alloantigen-specific CD8 high Treg could be induced and expanded from naive CD8 +CD25 - T cells at a large scale after 3 wk of culture without exogenous cytokines. These induced alloantigen-specific Treg were CD45RO + and CCR7 - memory cells, and they expressed Foxp3, CD25, CD27, CD28, and CD62L. The induction and expansion of CD8 high Treg by CD40-activated B cells were dependent on endogenously expressed IFN-γ, IL-2, IL-4, and CTLA-4. This approach may facilitate the clinical application of CD8 + Treg-based immunotherapy in transplantation and autoimmune diseases. Copyright © 2009 by The American Association of Immunologists, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/125232
ISSN
2015 Impact Factor: 4.985
2015 SCImago Journal Rankings: 3.549
ISI Accession Number ID
Funding AgencyGrant Number
University Research Committee
University of Hong Kong
Hong Kong SAR
People's Republic of China
Edward Sai-Kim Hotung Pediatric Education and Research Fund
University of Hong Kong Postgraduate Studentships
Funding Information:

This work was supported in part by Seed Funding for Basic Research. University Research Committee, University of Hong Kong, Hong Kong SAR, People's Republic of China (to W.T.); Edward Sai-Kim Hotung Pediatric Education and Research Fund (to Y.L.L. and W.T.); and the University of Hong Kong Postgraduate Studentships (to J.Z., G.Q.. P.L.C.. and H.M.).

References

 

DC FieldValueLanguage
dc.contributor.authorZheng, Jen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorQin, Gen_HK
dc.contributor.authorChan, PLen_HK
dc.contributor.authorMao, Hen_HK
dc.contributor.authorLam, KTen_HK
dc.contributor.authorLewis, DBen_HK
dc.contributor.authorLau, YLen_HK
dc.contributor.authorTu, Wen_HK
dc.date.accessioned2010-10-31T11:18:58Z-
dc.date.available2010-10-31T11:18:58Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Immunology, 2009, v. 183 n. 6, p. 3742-3750en_HK
dc.identifier.issn0022-1767en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125232-
dc.description.abstractAlthough recent studies have focused on CD4 + regulatory T cells (Treg), CD8 + Treg have also been reported to play important roles in the induction and maintenance of immune tolerance. Adoptive transfer of CD8 + Treg in rodents or induction of CD8 + Treg in humans can prevent or treat allograft rejection and autoimmune diseases. However, no approaches have been reported for the generation of human Ag-specific CD8 + Treg at a practical scale for clinical use. Here, we found that two novel CD8 + T cell subsets with different levels of CD8 surface expression, CD8 high and CD8 low, could be induced from naive CD8 + precursors in vitro by allogeneic CD40-activated B cells, whereas only CD8 high T cells were alloantigen-specific Treg with relatively poor alloantigen-specific cytotoxicity. Importantly, alloantigen-specific CD8 high Treg could be induced and expanded from naive CD8 +CD25 - T cells at a large scale after 3 wk of culture without exogenous cytokines. These induced alloantigen-specific Treg were CD45RO + and CCR7 - memory cells, and they expressed Foxp3, CD25, CD27, CD28, and CD62L. The induction and expansion of CD8 high Treg by CD40-activated B cells were dependent on endogenously expressed IFN-γ, IL-2, IL-4, and CTLA-4. This approach may facilitate the clinical application of CD8 + Treg-based immunotherapy in transplantation and autoimmune diseases. Copyright © 2009 by The American Association of Immunologists, Inc.en_HK
dc.languageengen_HK
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.orgen_HK
dc.relation.ispartofJournal of Immunologyen_HK
dc.subject.meshB-Lymphocytes - immunology-
dc.subject.meshCD8-Positive T-Lymphocytes - cytology - immunology-
dc.subject.meshCell Lineage - immunology-
dc.subject.meshIsoantigens - immunology-
dc.subject.meshT-Lymphocytes, Regulatory - cytology - immunology-
dc.titleEfficient induction and expansion of human alloantigen-specific CD8 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=0022-1767&volume=183&issue=6&spage=3742&epage=3750&date=2009&atitle=Efficient+induction+and+expansion+of+human+alloantigen-specific+CD8+regulatory+T+cells+from+naive+precursors+by+CD40-activated+B+cellsen_HK
dc.identifier.emailLiu, Y:yinpingl@hku.hken_HK
dc.identifier.emailMao, H:hwmau@hku.hken_HK
dc.identifier.emailLau, YL:lauylung@hkucc.hku.hken_HK
dc.identifier.emailTu, W:wwtu@hkucc.hku.hken_HK
dc.identifier.authorityLiu, Y=rp00269en_HK
dc.identifier.authorityMao, H=rp01595en_HK
dc.identifier.authorityLau, YL=rp00361en_HK
dc.identifier.authorityTu, W=rp00416en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.4049/jimmunol.0901329en_HK
dc.identifier.pmid19684082-
dc.identifier.scopuseid_2-s2.0-70349339392en_HK
dc.identifier.hkuros179381en_HK
dc.identifier.hkuros163412-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70349339392&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume183en_HK
dc.identifier.issue6en_HK
dc.identifier.spage3742en_HK
dc.identifier.epage3750en_HK
dc.identifier.isiWOS:000270179700025-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZheng, J=55217878700en_HK
dc.identifier.scopusauthoridLiu, Y=35240639600en_HK
dc.identifier.scopusauthoridQin, G=35085420900en_HK
dc.identifier.scopusauthoridChan, PL=25631876900en_HK
dc.identifier.scopusauthoridMao, H=25632489000en_HK
dc.identifier.scopusauthoridLam, KT=25630903400en_HK
dc.identifier.scopusauthoridLewis, DB=7404750928en_HK
dc.identifier.scopusauthoridLau, YL=7201403380en_HK
dc.identifier.scopusauthoridTu, W=7006479236en_HK

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