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Article: Phosphoantigen-expanded human γδ T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses

TitlePhosphoantigen-expanded human γδ T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses
Authors
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://jid.oxfordjournals.org
Citation
Journal Of Infectious Diseases, 2009, v. 200 n. 6, p. 858-865 How to Cite?
AbstractBackground. Influenza virus is a cause of substantial annual morbidity and mortality worldwide. The potential emergence of a new pandemic strain (eg, avian influenza virus) is a major concern. Currently available vaccines and anti-influenza drugs have limited effectiveness for influenza virus infections, especially for new pandemic strains. Therefore, there is an acute need to develop alternative strategies for influenza therapy, γδ T cells have potent antiviral activities against different viruses, but no data are available concerning their antiviral activity against influenza viruses. Methods. In this study, we used virus-infected primary human monocyte-derived macrophages (MDMs) to examine the antiviral activity of phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human Vγ9Vδ2 T cells against influenza viruses. Results. Vγ9Vδ2 T cells were selectively activated and expanded by IPP from peripheral blood mononuclear cells. IPP-expanded Vγ9Vδ2 T cells efficiently killed MDMs infected with human (H1N1) or avian (H9N2 or H5N1) influenza virus and significantly inhibited viral replication. The cytotoxicity of Vγ9Vδ2 T cells against influenza virus-infected MDMs was dependent on NKG2D activation and was mediated by Fas-Fas ligand and perforin-granzyme B pathways. Conclusion. Our findings suggest a potentially novel therapeutic approach to seasonal, zoonotic avian, and pandemic influenza-the use of phosphoantigens to activate γδ T cells against influenza virus infections. © 2009 by Infectious Diseases Society of America. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/78874
ISSN
2015 Impact Factor: 6.344
2015 SCImago Journal Rankings: 4.000
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU 777407M
HKU 777108M
Control of Infectious Diseases, Hong Kong government07060482
University Grants Committee, Hong KongAoE/M-12/06
University of Hong Kong
Edward Sai Kim Hotung Paediatric Education and Research Fund
Funding Information:

Research Grants Council of Hong Kong (General Research Fund; grants HKU 777407M and HKU 777108M to W. T.); Research Fund for the Control of Infectious Diseases, Hong Kong government (grant 07060482 to W. T.); University Grants Committee, Hong Kong (grant AoE/M-12/06 to Y.-L.L. and W. T.); University of Hong Kong ( postgraduate studentships to G. Q., H. M., J.Z., and P.L. C.); Edward Sai Kim Hotung Paediatric Education and Research Fund (G. Q., H. M., J.Z., and P.-L.C.).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorQin, Gen_HK
dc.contributor.authorMao, Hen_HK
dc.contributor.authorZheng, Jen_HK
dc.contributor.authorSia, SFen_HK
dc.contributor.authorLiu, Yen_HK
dc.contributor.authorChan, PLen_HK
dc.contributor.authorLam, KTen_HK
dc.contributor.authorMalik Peiris, JSen_HK
dc.contributor.authorLau, YLen_HK
dc.contributor.authorTu, Wen_HK
dc.date.accessioned2010-09-06T07:47:52Z-
dc.date.available2010-09-06T07:47:52Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Infectious Diseases, 2009, v. 200 n. 6, p. 858-865en_HK
dc.identifier.issn0022-1899en_HK
dc.identifier.urihttp://hdl.handle.net/10722/78874-
dc.description.abstractBackground. Influenza virus is a cause of substantial annual morbidity and mortality worldwide. The potential emergence of a new pandemic strain (eg, avian influenza virus) is a major concern. Currently available vaccines and anti-influenza drugs have limited effectiveness for influenza virus infections, especially for new pandemic strains. Therefore, there is an acute need to develop alternative strategies for influenza therapy, γδ T cells have potent antiviral activities against different viruses, but no data are available concerning their antiviral activity against influenza viruses. Methods. In this study, we used virus-infected primary human monocyte-derived macrophages (MDMs) to examine the antiviral activity of phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human Vγ9Vδ2 T cells against influenza viruses. Results. Vγ9Vδ2 T cells were selectively activated and expanded by IPP from peripheral blood mononuclear cells. IPP-expanded Vγ9Vδ2 T cells efficiently killed MDMs infected with human (H1N1) or avian (H9N2 or H5N1) influenza virus and significantly inhibited viral replication. The cytotoxicity of Vγ9Vδ2 T cells against influenza virus-infected MDMs was dependent on NKG2D activation and was mediated by Fas-Fas ligand and perforin-granzyme B pathways. Conclusion. Our findings suggest a potentially novel therapeutic approach to seasonal, zoonotic avian, and pandemic influenza-the use of phosphoantigens to activate γδ T cells against influenza virus infections. © 2009 by Infectious Diseases Society of America. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://jid.oxfordjournals.orgen_HK
dc.relation.ispartofJournal of Infectious Diseasesen_HK
dc.subject.meshInfluenza A Virus, H1N1 Subtype - physiology-
dc.subject.meshInfluenza A Virus, H5N1 Subtype - physiology-
dc.subject.meshInfluenza A Virus, H9N2 Subtype - physiology-
dc.subject.meshReceptors, Antigen, T-Cell, gamma-delta - immunology-
dc.subject.meshT-Lymphocytes - immunology - metabolism-
dc.titlePhosphoantigen-expanded human γδ T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza virusesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-1899&volume=200&spage=858&epage=865&date=2009&atitle=Phosphoantigen-expanded+gammadelta+T+cells+display+potent+cytotoxicity+against+human+and+avian+influenza+virus-infected+monocyte-derived+macrophagesen_HK
dc.identifier.emailMao, H: hwmau@hku.hken_HK
dc.identifier.emailLiu, Y: yinpingl@hku.hken_HK
dc.identifier.emailMalik Peiris, JS: malik@hkucc.hku.hken_HK
dc.identifier.emailLau, YL: lauylung@hku.hken_HK
dc.identifier.emailTu, W: wwtu@hku.hken_HK
dc.identifier.authorityMao, H=rp01595en_HK
dc.identifier.authorityLiu, Y=rp00269en_HK
dc.identifier.authorityMalik Peiris, JS=rp00410en_HK
dc.identifier.authorityLau, YL=rp00361en_HK
dc.identifier.authorityTu, W=rp00416en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1086/605413en_HK
dc.identifier.pmid19656068-
dc.identifier.scopuseid_2-s2.0-70349417911en_HK
dc.identifier.hkuros163411en_HK
dc.identifier.hkuros179382en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70349417911&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume200en_HK
dc.identifier.issue6en_HK
dc.identifier.spage858en_HK
dc.identifier.epage865en_HK
dc.identifier.eissn0022-1899-
dc.identifier.isiWOS:000269034200005-
dc.publisher.placeUnited Statesen_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.projectHumanized mouse as a model to study the antiviral activity of human gammadelta-T cells against human and avian influenza A viruses in vivo-
dc.relation.projectControl of Pandemic and Inter-pandemic Influenza-
dc.identifier.scopusauthoridQin, G=35085420900en_HK
dc.identifier.scopusauthoridMao, H=25632489000en_HK
dc.identifier.scopusauthoridZheng, J=55217878700en_HK
dc.identifier.scopusauthoridSia, SF=8574447900en_HK
dc.identifier.scopusauthoridLiu, Y=35240639600en_HK
dc.identifier.scopusauthoridChan, PL=25631876900en_HK
dc.identifier.scopusauthoridLam, KT=25630903400en_HK
dc.identifier.scopusauthoridMalik Peiris, JS=7005486823en_HK
dc.identifier.scopusauthoridLau, YL=7201403380en_HK
dc.identifier.scopusauthoridTu, W=7006479236en_HK
dc.identifier.citeulike5377209-

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