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Article: The potency of allospecific tregs cells appears to correlate with T cell receptor functional avidity
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TitleThe potency of allospecific tregs cells appears to correlate with T cell receptor functional avidity
 
AuthorsTsang, JYS2
Ratnasothy, K1
Li, D
Chen, Y2
Bucy, RP3
Lau, KF4
Smyth, L1
Lombardi, G1
Lechler, R1
Tam, PKH
 
Issue Date2011
 
PublisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/AJT
 
CitationAmerican Journal of Transplantation, 2011, v. 11 n. 8, p. 1610-1620 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1600-6143.2011.03650.x
 
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.
 
ISSN1600-6135
2012 Impact Factor: 6.192
2012 SCImago Journal Rankings: 2.575
 
DOIhttp://dx.doi.org/10.1111/j.1600-6143.2011.03650.x
 
ISI Accession Number IDWOS:000293340900014
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 FieldValue
dc.contributor.authorTsang, JYS
 
dc.contributor.authorRatnasothy, K
 
dc.contributor.authorLi, D
 
dc.contributor.authorChen, Y
 
dc.contributor.authorBucy, RP
 
dc.contributor.authorLau, KF
 
dc.contributor.authorSmyth, L
 
dc.contributor.authorLombardi, G
 
dc.contributor.authorLechler, R
 
dc.contributor.authorTam, PKH
 
dc.date.accessioned2011-09-23T05:55:16Z
 
dc.date.available2011-09-23T05:55:16Z
 
dc.date.issued2011
 
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.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationAmerican Journal of Transplantation, 2011, v. 11 n. 8, p. 1610-1620 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1600-6143.2011.03650.x
 
dc.identifier.citeulike9649161
 
dc.identifier.doihttp://dx.doi.org/10.1111/j.1600-6143.2011.03650.x
 
dc.identifier.epage1620
 
dc.identifier.hkuros193248
 
dc.identifier.isiWOS:000293340900014
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.identifier.issn1600-6135
2012 Impact Factor: 6.192
2012 SCImago Journal Rankings: 2.575
 
dc.identifier.issue8
 
dc.identifier.openurl
 
dc.identifier.pmid21797973
 
dc.identifier.scopuseid_2-s2.0-79961049730
 
dc.identifier.spage1610
 
dc.identifier.urihttp://hdl.handle.net/10722/139754
 
dc.identifier.volume11
 
dc.languageeng
 
dc.publisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/AJT
 
dc.publisher.placeDenmark
 
dc.relation.ispartofAmerican Journal of Transplantation
 
dc.rightsThe definitive version is available at www.blackwell-synergy.com
 
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 avidity
 
dc.typeArticle
 
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<contributor.author>Li, D</contributor.author>
<contributor.author>Chen, Y</contributor.author>
<contributor.author>Bucy, RP</contributor.author>
<contributor.author>Lau, KF</contributor.author>
<contributor.author>Smyth, L</contributor.author>
<contributor.author>Lombardi, G</contributor.author>
<contributor.author>Lechler, R</contributor.author>
<contributor.author>Tam, PKH</contributor.author>
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<description.abstract>CD4(+) 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.</description.abstract>
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Author Affiliations
  1. King's College London
  2. The University of Hong Kong
  3. University of Alabama
  4. Chinese University of Hong Kong