Sex and Age Impact CD4+ T Cell Susceptibility to HIV In Vitro through Cell Activation Dynamics
Cellular composition and the responsiveness of the immune system evolve upon aging and are influenced by biological sex. CD4+ T cells from women living with HIV exhibit a decreased viral replication ex vivo compared to men’s. We, thus, hypothesized that these findings could be recapitulated in vitro...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/23/2689 |
| _version_ | 1797400332640190464 |
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| author | Ludivine Brandt Paolo Angelino Raquel Martinez Sara Cristinelli Angela Ciuffi |
| author_facet | Ludivine Brandt Paolo Angelino Raquel Martinez Sara Cristinelli Angela Ciuffi |
| author_sort | Ludivine Brandt |
| collection | DOAJ |
| description | Cellular composition and the responsiveness of the immune system evolve upon aging and are influenced by biological sex. CD4+ T cells from women living with HIV exhibit a decreased viral replication ex vivo compared to men’s. We, thus, hypothesized that these findings could be recapitulated in vitro and infected primary CD4+ T cells with HIV-based vectors pseudotyped with VSV-G or HIV envelopes. We used cells isolated from twenty donors to interrogate the effect of sex and age on permissiveness over a six-day activation kinetics. Our data identified an increased permissiveness to HIV between 24 and 72 h post-stimulation. Sex- and age-based analyses at these time points showed an increased susceptibility to HIV of the cells isolated from males and from donors over 50 years of age, respectively. A parallel assessment of surface markers’ expression revealed higher frequencies of activation marker CD69 and of immune checkpoint inhibitors (PD-1 and CTLA-4) in the cells from highly permissive donors. Furthermore, positive correlations were identified between the expression kinetics of CD69, PD-1 and CTLA-4 and HIV expression kinetics. The cell population heterogeneity was assessed using a single-cell RNA-Seq analysis and no cell subtype enrichment was identified according to sex. Finally, transcriptomic analyses further highlighted the role of activation in those differences with enriched activation and cell cycle gene sets in male and older female cells. Altogether, this study brought further evidence about the individual features affecting HIV replication at the cellular level and should be considered in latency reactivation studies for an HIV cure. |
| first_indexed | 2024-03-09T01:54:00Z |
| format | Article |
| id | doaj.art-94921f04c4664331ad77c08c67edecdc |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T01:54:00Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-94921f04c4664331ad77c08c67edecdc2023-12-08T15:13:04ZengMDPI AGCells2073-44092023-11-011223268910.3390/cells12232689Sex and Age Impact CD4+ T Cell Susceptibility to HIV In Vitro through Cell Activation DynamicsLudivine Brandt0Paolo Angelino1Raquel Martinez2Sara Cristinelli3Angela Ciuffi4Institute of Microbiology, Lausanne University Hospital and University of Lausanne, 1010 Lausanne, SwitzerlandInstitute of Microbiology, Lausanne University Hospital and University of Lausanne, 1010 Lausanne, SwitzerlandInstitute of Microbiology, Lausanne University Hospital and University of Lausanne, 1010 Lausanne, SwitzerlandInstitute of Microbiology, Lausanne University Hospital and University of Lausanne, 1010 Lausanne, SwitzerlandInstitute of Microbiology, Lausanne University Hospital and University of Lausanne, 1010 Lausanne, SwitzerlandCellular composition and the responsiveness of the immune system evolve upon aging and are influenced by biological sex. CD4+ T cells from women living with HIV exhibit a decreased viral replication ex vivo compared to men’s. We, thus, hypothesized that these findings could be recapitulated in vitro and infected primary CD4+ T cells with HIV-based vectors pseudotyped with VSV-G or HIV envelopes. We used cells isolated from twenty donors to interrogate the effect of sex and age on permissiveness over a six-day activation kinetics. Our data identified an increased permissiveness to HIV between 24 and 72 h post-stimulation. Sex- and age-based analyses at these time points showed an increased susceptibility to HIV of the cells isolated from males and from donors over 50 years of age, respectively. A parallel assessment of surface markers’ expression revealed higher frequencies of activation marker CD69 and of immune checkpoint inhibitors (PD-1 and CTLA-4) in the cells from highly permissive donors. Furthermore, positive correlations were identified between the expression kinetics of CD69, PD-1 and CTLA-4 and HIV expression kinetics. The cell population heterogeneity was assessed using a single-cell RNA-Seq analysis and no cell subtype enrichment was identified according to sex. Finally, transcriptomic analyses further highlighted the role of activation in those differences with enriched activation and cell cycle gene sets in male and older female cells. Altogether, this study brought further evidence about the individual features affecting HIV replication at the cellular level and should be considered in latency reactivation studies for an HIV cure.https://www.mdpi.com/2073-4409/12/23/2689HIV-1HIV susceptibilityimmune activationsex differencesage differences |
| spellingShingle | Ludivine Brandt Paolo Angelino Raquel Martinez Sara Cristinelli Angela Ciuffi Sex and Age Impact CD4+ T Cell Susceptibility to HIV In Vitro through Cell Activation Dynamics Cells HIV-1 HIV susceptibility immune activation sex differences age differences |
| title | Sex and Age Impact CD4+ T Cell Susceptibility to HIV In Vitro through Cell Activation Dynamics |
| title_full | Sex and Age Impact CD4+ T Cell Susceptibility to HIV In Vitro through Cell Activation Dynamics |
| title_fullStr | Sex and Age Impact CD4+ T Cell Susceptibility to HIV In Vitro through Cell Activation Dynamics |
| title_full_unstemmed | Sex and Age Impact CD4+ T Cell Susceptibility to HIV In Vitro through Cell Activation Dynamics |
| title_short | Sex and Age Impact CD4+ T Cell Susceptibility to HIV In Vitro through Cell Activation Dynamics |
| title_sort | sex and age impact cd4 t cell susceptibility to hiv in vitro through cell activation dynamics |
| topic | HIV-1 HIV susceptibility immune activation sex differences age differences |
| url | https://www.mdpi.com/2073-4409/12/23/2689 |
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