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Article: ICOS regulates the generation and function of human CD4+ Treg in a CTLA-4 dependent manner

TitleICOS regulates the generation and function of human CD4+ Treg in a CTLA-4 dependent manner
Authors
Issue Date2013
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
PLoS One, 2013, v. 8 n. 12, p. e82203 How to Cite?
AbstractInducible co-stimulator (ICOS) is a member of CD28/Cytotoxic T-lymphocyte Antigen-4 (CTLA-4) family and broadly expressed in activated CD4+ T cells and induced regulatory CD4+ T cells (CD4+ iTreg). ICOS-related signal pathway could be activated by the interaction between ICOS and its ligand (ICOSL). In our previous work, we established a cost-effective system to generate a novel human allo-antigen specific CD4hi Treg by co-culturing their naïve precursors with allogeneic CD40-activated B cells in vitro. Here we investigate the role of ICOS in the generation and function of CD4hi Treg by interrupting ICOS-ICOSL interaction with ICOS-Ig. It is found that blockade of ICOS-ICOSL interaction impairs the induction and expansion of CD4hi Treg induced by allogeneic CD40-activated B cells. More importantly, CD4hi Treg induced with the addition of ICOS-Ig exhibits decreased suppressive capacity on alloantigen-specific responses. Dysfunction of CD4hi Treg induced with ICOS-Ig is accompanied with its decreased exocytosis and surface CTLA-4 expression. Through inhibiting endocytosis with E64 and pepstatin A, surface CTLA-4 expression and suppressive functions of induced CD4hi Treg could be partly reversed. Conclusively, our results demonstrate the beneficial role of ICOS-ICOSL signal pathway in the generation and function of CD4hi Treg and uncover a novel relationship between ICOS and CTLA-4. © 2013 zheng et al.
Persistent Identifierhttp://hdl.handle.net/10722/193882
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZheng, Jen_US
dc.contributor.authorChan, PLen_US
dc.contributor.authorLiu, Yen_US
dc.contributor.authorQin, Gen_US
dc.contributor.authorXiang, Zen_US
dc.contributor.authorLam, KTen_US
dc.contributor.authorLewis, DBen_US
dc.contributor.authorLau, YLen_US
dc.contributor.authorTu, Wen_US
dc.date.accessioned2014-01-28T06:31:28Z-
dc.date.available2014-01-28T06:31:28Z-
dc.date.issued2013en_US
dc.identifier.citationPLoS One, 2013, v. 8 n. 12, p. e82203en_US
dc.identifier.issn1932-6203-
dc.identifier.urihttp://hdl.handle.net/10722/193882-
dc.description.abstractInducible co-stimulator (ICOS) is a member of CD28/Cytotoxic T-lymphocyte Antigen-4 (CTLA-4) family and broadly expressed in activated CD4+ T cells and induced regulatory CD4+ T cells (CD4+ iTreg). ICOS-related signal pathway could be activated by the interaction between ICOS and its ligand (ICOSL). In our previous work, we established a cost-effective system to generate a novel human allo-antigen specific CD4hi Treg by co-culturing their naïve precursors with allogeneic CD40-activated B cells in vitro. Here we investigate the role of ICOS in the generation and function of CD4hi Treg by interrupting ICOS-ICOSL interaction with ICOS-Ig. It is found that blockade of ICOS-ICOSL interaction impairs the induction and expansion of CD4hi Treg induced by allogeneic CD40-activated B cells. More importantly, CD4hi Treg induced with the addition of ICOS-Ig exhibits decreased suppressive capacity on alloantigen-specific responses. Dysfunction of CD4hi Treg induced with ICOS-Ig is accompanied with its decreased exocytosis and surface CTLA-4 expression. Through inhibiting endocytosis with E64 and pepstatin A, surface CTLA-4 expression and suppressive functions of induced CD4hi Treg could be partly reversed. Conclusively, our results demonstrate the beneficial role of ICOS-ICOSL signal pathway in the generation and function of CD4hi Treg and uncover a novel relationship between ICOS and CTLA-4. © 2013 zheng et al.-
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action-
dc.relation.ispartofPLoS Oneen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleICOS regulates the generation and function of human CD4+ Treg in a CTLA-4 dependent manneren_US
dc.typeArticleen_US
dc.identifier.emailZheng, J: teddy629@hku.hken_US
dc.identifier.emailChan, PL: pandacha@hku.hken_US
dc.identifier.emailLiu, Y: yinpingl@hku.hken_US
dc.identifier.emailLam, KT: ktlama@graduate.hku.hken_US
dc.identifier.emailLau, YL: lauylung@hku.hken_US
dc.identifier.emailTu, W: wwtu@hku.hken_US
dc.identifier.authorityLiu, Y=rp00269en_US
dc.identifier.authorityLau, YL=rp00361en_US
dc.identifier.authorityTu, W=rp00416en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0082203en_US
dc.identifier.pmid24312642-
dc.identifier.pmcidPMC3846688-
dc.identifier.scopuseid_2-s2.0-84891607732-
dc.identifier.hkuros227394en_US
dc.identifier.volume8en_US
dc.identifier.issue12-
dc.identifier.spagee82203en_US
dc.identifier.epagee82203en_US
dc.identifier.isiWOS:000327944500124-
dc.publisher.placeUnited States-

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