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Article: Persistent lentivirus infection induces early myeloid suppressor cells expansion to subvert protective memory CD8 T cell response✰,✰✰

TitlePersistent lentivirus infection induces early myeloid suppressor cells expansion to subvert protective memory CD8 T cell response✰,✰✰
Authors
KeywordsPersistent virus infection
Vaccine
Memory cd8 t cell response
MDSCs
T cell exhaustion
Issue Date2020
PublisherElsevier: Creative Commons. The Journal's web site is located at http://www.ebiomedicine.com
Citation
EBioMedicine, 2020, v. 60, p. article no. 103008 How to Cite?
AbstractBackground: Memory CD8+T cell responses play an essential role in protection against persistent infection. However, HIV-1 evades vaccine-induced memory CD8+T cell response by mechanisms that are not fully understood. Methods: We analyzed the temporal dynamics of CD8+T cell recall activity and function during EcoHIV infection in a potent PD1-based vaccine immunized immunocompetent mice. Findings: Upon intraperitoneal EcoHIV infection, high levels of HIV-1 GAG-specific CD8+T lymphocytes recall response reduced EcoHIV-infected cells significantly. However, this protective effect diminished quickly after seven days, followed by a rapid reduction of GAG-specific CD8+T cell number and activity, and viral persistence. Mechanistically, EcoHIV activated dendritic cells (DCs) and myeloid cells. Myeloid cells were infected and rapidly expanded, exhibiting elevated PD-L1/-L2 expression and T cell suppressive function before day 7, and were resistant to CD8+T cell-mediated apoptosis. Depletion of myeloid-derived suppressor cells (MDSCs) reduced EcoHIV infection and boosted T cell responses. Interpretation: This study provides an overview of the temporal interplay of persistent virus, DCs, MDSCs and antigen-specific CD8+T cells during acute infection. We identify MDSCs as critical gatekeepers that restrain antiviral T cell memory responses, and highlight MDSCs as an important target for developing effective vaccines against chronic human infections.
Persistent Identifierhttp://hdl.handle.net/10722/289792
ISSN
2023 Impact Factor: 9.7
2023 SCImago Journal Rankings: 3.193
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, L-
dc.contributor.authorLin, Q-
dc.contributor.authorPeng, J-
dc.contributor.authorFang, J-
dc.contributor.authorTan, Z-
dc.contributor.authorTang, H-
dc.contributor.authorKwan, K-
dc.contributor.authorNishiura, K-
dc.contributor.authorLiang, J-
dc.contributor.authorKwok, H-
dc.contributor.authorDu, Z-
dc.contributor.authorSun, J-
dc.contributor.authorLiu, K-
dc.contributor.authorYuen, KY-
dc.contributor.authorWang, H-
dc.contributor.authorChen, Z-
dc.date.accessioned2020-10-22T08:17:32Z-
dc.date.available2020-10-22T08:17:32Z-
dc.date.issued2020-
dc.identifier.citationEBioMedicine, 2020, v. 60, p. article no. 103008-
dc.identifier.issn2352-3964-
dc.identifier.urihttp://hdl.handle.net/10722/289792-
dc.description.abstractBackground: Memory CD8+T cell responses play an essential role in protection against persistent infection. However, HIV-1 evades vaccine-induced memory CD8+T cell response by mechanisms that are not fully understood. Methods: We analyzed the temporal dynamics of CD8+T cell recall activity and function during EcoHIV infection in a potent PD1-based vaccine immunized immunocompetent mice. Findings: Upon intraperitoneal EcoHIV infection, high levels of HIV-1 GAG-specific CD8+T lymphocytes recall response reduced EcoHIV-infected cells significantly. However, this protective effect diminished quickly after seven days, followed by a rapid reduction of GAG-specific CD8+T cell number and activity, and viral persistence. Mechanistically, EcoHIV activated dendritic cells (DCs) and myeloid cells. Myeloid cells were infected and rapidly expanded, exhibiting elevated PD-L1/-L2 expression and T cell suppressive function before day 7, and were resistant to CD8+T cell-mediated apoptosis. Depletion of myeloid-derived suppressor cells (MDSCs) reduced EcoHIV infection and boosted T cell responses. Interpretation: This study provides an overview of the temporal interplay of persistent virus, DCs, MDSCs and antigen-specific CD8+T cells during acute infection. We identify MDSCs as critical gatekeepers that restrain antiviral T cell memory responses, and highlight MDSCs as an important target for developing effective vaccines against chronic human infections.-
dc.languageeng-
dc.publisherElsevier: Creative Commons. The Journal's web site is located at http://www.ebiomedicine.com-
dc.relation.ispartofEBioMedicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectPersistent virus infection-
dc.subjectVaccine-
dc.subjectMemory cd8 t cell response-
dc.subjectMDSCs-
dc.subjectT cell exhaustion-
dc.titlePersistent lentivirus infection induces early myeloid suppressor cells expansion to subvert protective memory CD8 T cell response✰,✰✰-
dc.typeArticle-
dc.identifier.emailLiu, L: liuli71@hkucc.hku.hk-
dc.identifier.emailTan, Z: zwtan@hku.hk-
dc.identifier.emailKwan, K: hallieky@hku.hk-
dc.identifier.emailKwok, H: hauyeek@hku.hk-
dc.identifier.emailDu, Z: duzl@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityLiu, L=rp00268-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityChen, Z=rp00243-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.ebiom.2020.103008-
dc.identifier.pmid32979832-
dc.identifier.pmcidPMC7519271-
dc.identifier.scopuseid_2-s2.0-85091484203-
dc.identifier.hkuros317239-
dc.identifier.volume60-
dc.identifier.spagearticle no. 103008-
dc.identifier.epagearticle no. 103008-
dc.identifier.isiWOS:000580572100032-
dc.publisher.placeNetherlands-
dc.identifier.issnl2352-3964-

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