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Article: The potency of allospecific tregs cells appears to correlate with T cell receptor functional avidity

TitleThe potency of allospecific tregs cells appears to correlate with T cell receptor functional avidity
Authors
Issue Date2011
PublisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/AJT
Citation
American Journal of Transplantation, 2011, v. 11 n. 8, p. 1610-1620 How to Cite?
AbstractCD4(+) CD25(+) regulatory T cells (T(reg) cells) are an attractive adoptive cell therapy in mediating transplantation tolerance. T-cell receptor (TcR) activation is critical for T(reg) function, suggesting that the TcR avidity of T(reg) cells used in therapy may affect the therapeutic outcome. To address this, we compared the regulatory capacity of T(reg) lines expressing TcRs derived from two TcR transgenic mice shown to have the same specificity but different functional avidities. T(reg) lines generated from CD4(+)CD25(+) T cells from C57BL/6 mice were transduced with one of either of these TcRs. The antigen specificity of the transduced T(reg) lines was confirmed in vitro. T(reg) lines expressing the TcR with higher functional avidity showed stronger suppressive capacity in a linked suppression model in vitro. Furthermore, the same T(reg) lines demonstrated a stronger proliferation in vivo following antigen exposure. Pretreatment of recipient BL/6 mice with these T(reg) cells, together with anti-CD8 antibody and Rapamycin therapies, prolonged survival of BALB/c skins, as compared with mice that received T(reg) lines with lower TcR avidity. Taken together, these data suggest that the TcR functional avidity may be important for T(reg) function. It highlights the fact that strategies to select T(reg) with higher functional avidity might be beneficial for immunotherapy in transplantation.
Persistent Identifierhttp://hdl.handle.net/10722/139754
ISSN
2014 Impact Factor: 5.683
2014 SCImago Journal Rankings: 2.514
ISI Accession Number ID
Funding AgencyGrant Number
HKU200807176199
British Heart Foundation
EU RISET Consortium
Funding Information:

This work was supported by HKU small project grant (200807176199), the British Heart Foundation and EU RISET Consortium.

 

DC FieldValueLanguage
dc.contributor.authorTsang, JYSen_US
dc.contributor.authorRatnasothy, Ken_US
dc.contributor.authorLi, Den_US
dc.contributor.authorChen, Yen_US
dc.contributor.authorBucy, RPen_US
dc.contributor.authorLau, KFen_US
dc.contributor.authorSmyth, Len_US
dc.contributor.authorLombardi, Gen_US
dc.contributor.authorLechler, Ren_US
dc.contributor.authorTam, PKHen_US
dc.date.accessioned2011-09-23T05:55:16Z-
dc.date.available2011-09-23T05:55:16Z-
dc.date.issued2011en_US
dc.identifier.citationAmerican Journal of Transplantation, 2011, v. 11 n. 8, p. 1610-1620en_US
dc.identifier.issn1600-6135en_US
dc.identifier.urihttp://hdl.handle.net/10722/139754-
dc.description.abstractCD4(+) CD25(+) regulatory T cells (T(reg) cells) are an attractive adoptive cell therapy in mediating transplantation tolerance. T-cell receptor (TcR) activation is critical for T(reg) function, suggesting that the TcR avidity of T(reg) cells used in therapy may affect the therapeutic outcome. To address this, we compared the regulatory capacity of T(reg) lines expressing TcRs derived from two TcR transgenic mice shown to have the same specificity but different functional avidities. T(reg) lines generated from CD4(+)CD25(+) T cells from C57BL/6 mice were transduced with one of either of these TcRs. The antigen specificity of the transduced T(reg) lines was confirmed in vitro. T(reg) lines expressing the TcR with higher functional avidity showed stronger suppressive capacity in a linked suppression model in vitro. Furthermore, the same T(reg) lines demonstrated a stronger proliferation in vivo following antigen exposure. Pretreatment of recipient BL/6 mice with these T(reg) cells, together with anti-CD8 antibody and Rapamycin therapies, prolonged survival of BALB/c skins, as compared with mice that received T(reg) lines with lower TcR avidity. Taken together, these data suggest that the TcR functional avidity may be important for T(reg) function. It highlights the fact that strategies to select T(reg) with higher functional avidity might be beneficial for immunotherapy in transplantation.-
dc.languageengen_US
dc.publisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/AJTen_US
dc.relation.ispartofAmerican Journal of Transplantationen_US
dc.rightsThe definitive version is available at www.blackwell-synergy.comen_US
dc.subject.meshAnimals-
dc.subject.meshBase Sequence-
dc.subject.meshDNA Primers-
dc.subject.meshFlow Cytometry-
dc.subject.meshT-Lymphocytes, Regulatory - immunology-
dc.titleThe potency of allospecific tregs cells appears to correlate with T cell receptor functional avidityen_US
dc.typeArticleen_US
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1600-6135&volume=&spage=&epage=&date=2011&atitle=The+potency+of+allospecific+tregs+cells+appears+to+correlate+with+T+cell+receptor+functional+avidityen_US
dc.identifier.emailTsang, JYS: jystsang@hku.hken_US
dc.identifier.emailChen, Y: ychenc@hku.hken_US
dc.identifier.emailLombardi, G: giovanna.lombardi@kcl.ac.uken_US
dc.identifier.emailLechler, R: robert.lechler@kcl.ac.uk-
dc.identifier.emailTam, PKH: paultam@hku.hk-
dc.identifier.authorityChen, Y=rp01318en_US
dc.identifier.authorityTam, PKH=rp00060en_US
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1600-6143.2011.03650.x-
dc.identifier.pmid21797973-
dc.identifier.scopuseid_2-s2.0-79961049730-
dc.identifier.hkuros193248en_US
dc.identifier.volume11-
dc.identifier.issue8-
dc.identifier.spage1610-
dc.identifier.epage1620-
dc.identifier.isiWOS:000293340900014-
dc.publisher.placeDenmark-
dc.identifier.citeulike9649161-

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