Characterization of HIV-induced remodeling reveals differences in infection susceptibility of memory CD4+ T cell subsets in vivo

Xie, Guorui; Luo, Xiaoyu; Ma, Tongcui; Frouard, Julie; Neidleman, Jason; Hoh, Rebecca; Deeks, Steven G.; Greene, Warner C.; Roan, Nadia R.

doi:10.1016/j.celrep.2021.109038

Cited by 17 publications

(30 citation statements)

References 16 publications

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“…Freshly isolated cells from blood and LN specimens were immediately treated with cisplatin (Sigma-Aldrich, St. Louis, MO, USA) as a live/dead marker and then fixed with paraformaldehyde as described previously (44)(45)(46)(47)(48)(49)(50). Briefly, a total of 6 x 10 6 cells were resuspended in 2 ml PBS (Rockland, Gilbertsville, PA, USA) with 2 mM EDTA (Corning, Corning, NY, USA).…”

Section: Preparation Of Cells For Cytofmentioning

confidence: 99%

“…Staining of cells for CyTOF analysis was conducted as previously described (44)(45)(46)(47)(48)(49)(50). To minimize cell loss, multiple cisplatin-treated samples were barcoded and combined using the Cell-ID 20-Plex Pd Barcoding Kit (Fluidigm, South San Francisco, CA, USA), according to the manufacturer's protocol.…”

Section: Cytof Staining and Data Acquisitionmentioning

confidence: 99%

“…CyTOF datasets were normalized and de-barcoded according to the manufacturer's protocol (Fluidigm, South San Francisco, CA, USA), as previously validated (44)(45)(46)(47)(48)(49)(50). FlowJo software (BD Biosciences) was used to gate for events corresponding to total T cells (live, singlet, CD19-CD14-CD33-CD3+), CD4+ T cells (live, singlet, CD19-CD14-CD33-CD3+CD8-), CD8+ T cells (live, singlet, CD19-CD14-CD33-CD3+CD8+), and NK cells (CD19-CD14-CD33-CD3-CD4-CD7+) among PBMC and LN specimens (Supplementary Figure S1).…”

Section: Cytof Data Analysismentioning

confidence: 99%

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Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells From HIV+ Controllers and ART-Suppressed Individuals

et al. 2022

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T and natural killer (NK) cells are effector cells with key roles in anti-HIV immunity, including in lymphoid tissues, the major site of HIV persistence. However, little is known about the features of these effector cells from people living with HIV (PLWH), particularly from those who initiated antiretroviral therapy (ART) during acute infection. Our study design was to use 42-parameter CyTOF to conduct deep phenotyping of paired blood- and lymph node (LN)-derived T and NK cells from three groups of HIV+ aviremic individuals: elite controllers (N = 5), and ART-suppressed individuals who had started therapy during chronic (N = 6) vs. acute infection (N = 8), the latter of which is associated with better outcomes. We found that acute-treated individuals are enriched for specific subsets of T and NK cells, including blood-derived CD56-CD16+ NK cells previously associated with HIV control, and LN-derived CD4+ T follicular helper cells with heightened expansion potential. An in-depth comparison of the features of the cells from blood vs. LNs of individuals from our cohort revealed that T cells from blood were more activated than those from LNs. By contrast, LNs were enriched for follicle-homing CXCR5+ CD8+ T cells, which expressed increased levels of inhibitory receptors and markers of survival and proliferation as compared to their CXCR5- counterparts. In addition, a subset of memory-like CD56brightTCF1+ NK cells was enriched in LNs relative to blood. These results together suggest unique T and NK cell features in acute-treated individuals, and highlight the importance of examining effector cells not only in blood but also the lymphoid tissue compartment, where the reservoir mostly persists, and where these cells take on distinct phenotypic features.

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Section: Preparation Of Cells For Cytofmentioning

confidence: 99%

Section: Cytof Staining and Data Acquisitionmentioning

confidence: 99%

Section: Cytof Data Analysismentioning

confidence: 99%

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Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells From HIV+ Controllers and ART-Suppressed Individuals

et al. 2022

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“…Freshly isolated cells from blood and LN specimens were immediately treated with cisplatin (Sigma-Aldrich, St. Louis, MO, USA) as a live/dead marker and then fixed with paraformaldehyde as described previously (Cavrois et al, 2017;Ma et al, 2020;Neidleman et al, 2020a;Neidleman et al, 2020b;Neidleman et al, 2021;Xie et al, 2021). Briefly, a total of 6 x 10 6 cells were resuspended in 2 ml PBS (Rockland, Gilbertsville, PA, USA) with 2 mM EDTA (Corning, Corning, NY, USA).…”

Section: Preparation Of Cells For Cytofmentioning

confidence: 99%

“…Staining of cells for CyTOF analysis was conducted as previously described (Cavrois et al, 2017;Ma et al, 2020;Neidleman et al, 2020a;Neidleman et al, 2020b;Neidleman et al, 2021;Xie et al, 2021). To minimize cell loss, multiple cisplatin-treated samples were barcoded and combined using the Cell-ID 20-Plex Pd Barcoding Kit (Fluidigm, South San Francisco, CA, USA), according to the manufacturer's protocol.…”

Section: Cytof Staining and Data Acquisitionmentioning

confidence: 99%

Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells from HIV+ Controllers and Non-Controllers

George

Luo

Neidleman

et al. 2021

Preprint

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T and natural killer (NK) cells are effector cells with key roles in anti-HIV immunity, including in lymphoid tissues, the major site of HIV persistence. In this study, we used 42-parameter CyTOF to conduct deep phenotyping of paired blood- and lymph node (LN)-derived T and NK cells from three groups of HIV+ aviremic individuals: elite controllers, and antiretroviral therapy (ART)-suppressed individuals who had started therapy during chronic vs. acute infection, the latter of which is associated with better outcomes. We found that acute-treated individuals are enriched for specific subsets of T and NK cells, including blood-derived CD56-CD16+ NK cells previously associated with HIV control, and LN-derived CD4+ T follicular helper cells with heightened expansion potential. An in-depth comparison of the features of the cells from blood vs. LNs of individuals from our cohort revealed that T cells from blood were more activated than those from LNs. By contrast, LNs were enriched for follicle-homing CXCR5+ CD8+ T cells, which expressed increased levels of inhibitory receptors and markers of survival and proliferation as compared to their CXCR5-counterparts. In addition, a subset of memory-like CD56brightTCF1+ NK cells was enriched in LNs relative to blood. These results together suggest unique T and NK cell features in acute-treated individuals, and highlight the importance of examining effector cells not only in blood but also the lymphoid tissue compartment, where the reservoir mostly persists, and where these cells take on distinct phenotypic features.

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Advances in HIV Research Using Mass Cytometry

George

Roan

2023

Curr HIV/AIDS Rep

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Purpose of Review This review describes how advances in CyTOF and high-dimensional analysis methods have furthered our understanding of HIV transmission, pathogenesis, persistence, and immunity. Recent Findings CyTOF has generated important insight on several aspects of HIV biology: (1) the differences between cells permissive to productive vs. latent HIV infection, and the HIV-induced remodeling of infected cells; (2) factors that contribute to the persistence of the long-term HIV reservoir, in both blood and tissues; and (3) the impact of HIV on the immune system, in the context of both uncontrolled and controlled infection. Summary CyTOF and high-dimensional analysis tools have enabled in-depth assessment of specific host antigens remodeled by HIV, and have revealed insights into the features of HIV-infected cells enabling them to survive and persist, and of the immune cells that can respond to and potentially control HIV replication. CyTOF and other related high-dimensional phenotyping approaches remain powerful tools for translational research, and applied HIV to cohort studies can inform on mechanisms of HIV pathogenesis and persistence, and potentially identify biomarkers for viral eradication or control.

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Characterization of HIV-induced remodeling reveals differences in infection susceptibility of memory CD4+ T cell subsets in vivo

Cited by 17 publications

References 16 publications

Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells From HIV+ Controllers and ART-Suppressed Individuals

Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells From HIV+ Controllers and ART-Suppressed Individuals

Deep Phenotypic Analysis of Blood and Lymphoid T and NK Cells from HIV+ Controllers and Non-Controllers

Advances in HIV Research Using Mass Cytometry

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