Dataset Information
Persistent lentivirus infection induces early myeloid suppressor cells expansion to subvert protective memory CD8 T cell response✰,✰✰.
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ABSTRACT: Background
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.Funding
Hong Kong Research Grant Council (T11-709/18-N, HKU5/CRF/13G), General Research Fund (17122915 and 17114114), Hong Kong Health and Medical Research Fund (11100752, 14130582, 16150662), Grant RGC-ANR A-HKU709/14, the San-Ming Project of Medicine (SZSM201512029), University Development Fund of the University of Hong Kong and Li Ka Shing Faculty of Medicine Matching Fund to HKU AIDS Institute.
SUBMITTER: Liu L
PROVIDER: S-EPMC7519271 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Persistent lentivirus infection induces early myeloid suppressor cells expansion to subvert protective memory CD8 T cell response<sup>✰,✰✰</sup>.
EBioMedicine 20200924
<h4>Background</h4>Memory CD8<sup>+</sup>T cell responses play an essential role in protection against persistent infection. However, HIV-1 evades vaccine-induced memory CD8<sup>+</sup>T cell response by mechanisms that are not fully understood.<h4>Methods</h4>We analyzed the temporal dynamics of CD8<sup>+</sup>T cell recall activity and function during EcoHIV infection in a potent PD1-based vaccine immunized immunocompetent mice.<h4>Findings</h4>Upon intraperitoneal EcoHIV infection, high level ...[more]