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Article: Generation of human Th1-like regulatory CD4 + T cells by an intrinsic IFN-γ- and T-bet-dependent pathway

TitleGeneration of human Th1-like regulatory CD4 + T cells by an intrinsic IFN-γ- and T-bet-dependent pathway
Authors
KeywordsB cells
Th1
Treg
Issue Date2011
PublisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.eji.de
Citation
European Journal Of Immunology, 2011, v. 41 n. 1, p. 128-139 How to Cite?
AbstractMurine Foxp3 + Treg have recently been shown to express T-bet, a transcription factor characteristic of Th1 effector cells. A human Treg phenotype equivalent has not been reported. Here, we show that naïve human CD4 + T cells incubated with low numbers of CD40-activated allogeneic B cells preferentially differentiate into alloantigen-specific CD4 hiCD25 hi Treg. These differentiated cells potently suppress effector T-cell responses and express T-bet, IFN-γ, and CXCR3, the features of Th1 effector cells. In contrast, co-culture of naïve CD4 + T cells with high numbers of allogeneic B cells results in CD4 +CD25 + T cells that promote, rather than inhibit, effector T-cell responses, demonstrating the plasticity of CD4 + T-cell differentiation in response to alloantigen-presenting B cells. The optimal accumulation of CD4 hiCD25 hi Treg induced using higher T cell:B cell co-culture ratios was dependent on the expression of T-bet and endogenously produced IFN-γ. Induction of Treg-mediated suppression function in the Treg population was not. As CXCR3 confers the preferential trafficking of T cells to tissue sites of IFN-γ, these human Th1-like Treg might be useful for modulating pathological Th1 effector responses, such as that occurring during graft-versus-host disease or graft rejection. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Persistent Identifierhttp://hdl.handle.net/10722/137470
ISSN
2015 Impact Factor: 4.179
2015 SCImago Journal Rankings: 2.568
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 777407M
HKU 777108M
University Grants Committee of the Hong Kong Special Administrative Region, ChinaAoE/M-12/06
Jeffrey Modell Foundation for Primary Immunodeficiency
Funding Information:

This work was supported in part by General Research Fund, Research Grants Council of Hong Kong (HKU 777407M, W. T. and HKU 777108M, W. T.); the Area of Excellence program supported by the University Grants Committee of the Hong Kong Special Administrative Region, China (Project No. AoE/M-12/06) (W. T. and Y.L.L.); and the Jeffrey Modell Foundation for Primary Immunodeficiency (D. B. L.).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorZheng, Jen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorQin, Gen_HK
dc.contributor.authorLam, KTen_HK
dc.contributor.authorGuan, Jen_HK
dc.contributor.authorXiang, Zen_HK
dc.contributor.authorLewis, DBen_HK
dc.contributor.authorLau, YLen_HK
dc.contributor.authorTu, Wen_HK
dc.date.accessioned2011-08-26T14:25:44Z-
dc.date.available2011-08-26T14:25:44Z-
dc.date.issued2011en_HK
dc.identifier.citationEuropean Journal Of Immunology, 2011, v. 41 n. 1, p. 128-139en_HK
dc.identifier.issn0014-2980en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137470-
dc.description.abstractMurine Foxp3 + Treg have recently been shown to express T-bet, a transcription factor characteristic of Th1 effector cells. A human Treg phenotype equivalent has not been reported. Here, we show that naïve human CD4 + T cells incubated with low numbers of CD40-activated allogeneic B cells preferentially differentiate into alloantigen-specific CD4 hiCD25 hi Treg. These differentiated cells potently suppress effector T-cell responses and express T-bet, IFN-γ, and CXCR3, the features of Th1 effector cells. In contrast, co-culture of naïve CD4 + T cells with high numbers of allogeneic B cells results in CD4 +CD25 + T cells that promote, rather than inhibit, effector T-cell responses, demonstrating the plasticity of CD4 + T-cell differentiation in response to alloantigen-presenting B cells. The optimal accumulation of CD4 hiCD25 hi Treg induced using higher T cell:B cell co-culture ratios was dependent on the expression of T-bet and endogenously produced IFN-γ. Induction of Treg-mediated suppression function in the Treg population was not. As CXCR3 confers the preferential trafficking of T cells to tissue sites of IFN-γ, these human Th1-like Treg might be useful for modulating pathological Th1 effector responses, such as that occurring during graft-versus-host disease or graft rejection. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.en_HK
dc.languageengen_US
dc.publisherWiley - V C H Verlag GmbH & Co KGaA. The Journal's web site is located at http://www.eji.deen_HK
dc.relation.ispartofEuropean Journal of Immunologyen_HK
dc.subjectB cellsen_HK
dc.subjectTh1en_HK
dc.subjectTregen_HK
dc.subject.meshB-Lymphocytes - immunology-
dc.subject.meshInterferon-gamma - immunology-
dc.subject.meshT-Box Domain Proteins - immunology-
dc.subject.meshT-Lymphocytes, Regulatory - immunology-
dc.subject.meshTh1 Cells - immunology-
dc.titleGeneration of human Th1-like regulatory CD4 + T cells by an intrinsic IFN-γ- and T-bet-dependent pathwayen_HK
dc.typeArticleen_HK
dc.identifier.emailLiu, Y:yinpingl@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.authorityLau, YL=rp00361en_HK
dc.identifier.authorityTu, W=rp00416en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/eji.201040724en_HK
dc.identifier.pmid21182084-
dc.identifier.scopuseid_2-s2.0-78650374915en_HK
dc.identifier.hkuros191485en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78650374915&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume41en_HK
dc.identifier.issue1en_HK
dc.identifier.spage128en_HK
dc.identifier.epage139en_HK
dc.identifier.isiWOS:000285933000014-
dc.publisher.placeGermanyen_HK
dc.relation.projectThe Role of Natural Killer Cells in the Pathogenesis of Avian Influenza Virus Infection-
dc.relation.projectImmune defense of human gammadelta-T cells against Influenza a viruses-
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridZheng, J=55217878700en_HK
dc.identifier.scopusauthoridLiu, Y=35240639600en_HK
dc.identifier.scopusauthoridQin, G=35085420900en_HK
dc.identifier.scopusauthoridLam, KT=25630903400en_HK
dc.identifier.scopusauthoridGuan, J=36243371100en_HK
dc.identifier.scopusauthoridXiang, Z=37032263900en_HK
dc.identifier.scopusauthoridLewis, DB=7404750928en_HK
dc.identifier.scopusauthoridLau, YL=7201403380en_HK
dc.identifier.scopusauthoridTu, W=7006479236en_HK

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