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Article: CD137 costimulation enhances the antiviral activity of Vγ9Vδ2-T cells against influenza virus

TitleCD137 costimulation enhances the antiviral activity of Vγ9Vδ2-T cells against influenza virus
Authors
Keywordsadaptive immunity
animal cell
animal experiment
animal model
animal tissue
Issue Date2020
PublisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/sigtrans/
Citation
Signal Transduction and Targeted Therapy, 2020, v. 5, p. article no. 74 How to Cite?
AbstractInfluenza epidemics and pandemics are constant threats to global public health. Although strategies including vaccines and antiviral drugs have achieved great advances in controlling influenza virus infection, the efficacy of these strategies is limited by the highly frequent mutations in the viral genome and the emergence of drug-resistant strains. Our previous study indicated that boosting the immunity of human Vγ9Vδ2-T cells with the phosphoantigen pamidronate could be a therapeutic strategy to treat seasonal and avian influenza virus infections. However, one notable drawback of γδ-T cell-based immunotherapy is the rapid exhaustion of proliferation and effector responses due to repeated treatments with phosphoantigens. Here, we found that the expression of CD137 was inducible in Vγ9Vδ2-T cells following antigenic stimulation. CD137+ Vγ9Vδ2-T cells displayed more potent antiviral activity against influenza virus than their CD137- counterparts in vitro and in Rag2-/- γc-/- mice. We further demonstrated that CD137 costimulation was essential for Vγ9Vδ2-T cell activation, proliferation, survival and effector functions. In humanized mice reconstituted with human peripheral blood mononuclear cells, CD137 costimulation with a recombinant human CD137L protein boosted the therapeutic effects of pamidronate against influenza virus. Our study provides a novel strategy of targeting CD137 to improve the efficacy of Vγ9Vδ2-T cell-based immunotherapy.
Persistent Identifierhttp://hdl.handle.net/10722/289152
ISSN
2023 Impact Factor: 40.8
2023 SCImago Journal Rankings: 8.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorPei, Y-
dc.contributor.authorWEN, K-
dc.contributor.authorXiang, Z-
dc.contributor.authorHUANG, C-
dc.contributor.authorWang, X-
dc.contributor.authorMU, X-
dc.contributor.authorWen, L-
dc.contributor.authorLiu, Y-
dc.contributor.authorTu, W-
dc.date.accessioned2020-10-22T08:08:33Z-
dc.date.available2020-10-22T08:08:33Z-
dc.date.issued2020-
dc.identifier.citationSignal Transduction and Targeted Therapy, 2020, v. 5, p. article no. 74-
dc.identifier.issn2059-3635-
dc.identifier.urihttp://hdl.handle.net/10722/289152-
dc.description.abstractInfluenza epidemics and pandemics are constant threats to global public health. Although strategies including vaccines and antiviral drugs have achieved great advances in controlling influenza virus infection, the efficacy of these strategies is limited by the highly frequent mutations in the viral genome and the emergence of drug-resistant strains. Our previous study indicated that boosting the immunity of human Vγ9Vδ2-T cells with the phosphoantigen pamidronate could be a therapeutic strategy to treat seasonal and avian influenza virus infections. However, one notable drawback of γδ-T cell-based immunotherapy is the rapid exhaustion of proliferation and effector responses due to repeated treatments with phosphoantigens. Here, we found that the expression of CD137 was inducible in Vγ9Vδ2-T cells following antigenic stimulation. CD137+ Vγ9Vδ2-T cells displayed more potent antiviral activity against influenza virus than their CD137- counterparts in vitro and in Rag2-/- γc-/- mice. We further demonstrated that CD137 costimulation was essential for Vγ9Vδ2-T cell activation, proliferation, survival and effector functions. In humanized mice reconstituted with human peripheral blood mononuclear cells, CD137 costimulation with a recombinant human CD137L protein boosted the therapeutic effects of pamidronate against influenza virus. Our study provides a novel strategy of targeting CD137 to improve the efficacy of Vγ9Vδ2-T cell-based immunotherapy.-
dc.languageeng-
dc.publisherNature Research (part of Springer Nature): Fully open access journals. The Journal's web site is located at http://www.nature.com/sigtrans/-
dc.relation.ispartofSignal Transduction and Targeted Therapy-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectadaptive immunity-
dc.subjectanimal cell-
dc.subjectanimal experiment-
dc.subjectanimal model-
dc.subjectanimal tissue-
dc.titleCD137 costimulation enhances the antiviral activity of Vγ9Vδ2-T cells against influenza virus-
dc.typeArticle-
dc.identifier.emailPei, Y: peiyujun@HKUCC-COM.hku.hk-
dc.identifier.emailWang, X: xweiwang@connect.hku.hk-
dc.identifier.emailLiu, Y: yinpingl@hku.hk-
dc.identifier.emailTu, W: wwtu@hku.hk-
dc.identifier.authorityLiu, Y=rp00269-
dc.identifier.authorityTu, W=rp00416-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41392-020-0174-2-
dc.identifier.pmid32488072-
dc.identifier.pmcidPMC7266814-
dc.identifier.scopuseid_2-s2.0-85085709000-
dc.identifier.hkuros316595-
dc.identifier.volume5-
dc.identifier.spagearticle no. 74-
dc.identifier.epagearticle no. 74-
dc.identifier.isiWOS:000537437300001-
dc.publisher.placeUnited States-
dc.identifier.issnl2059-3635-

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