Selective loss of CD107a TIGIT+ memory HIV-1-specific CD8+ T cells in PLWH over a decade of ART
- IrsiCaixa AIDS Research Institute, Spain
- Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain
- Pathology Department, Case Western Reserve University, United States
- Lluita contra la SIDA Foundation, Hospital Universitari Germans Trias i Pujol, Spain
- Infectious Diseases Department, Hospital Universitari Germans Trias i Pujol, Spain
- Germans Trias i Pujol Research Institute (IGTP), Spain
- Faculty of Medicine, University of Vic - Central University of Catalonia (UVic-UCC), Spain
- CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Spain
Figures
Figure 1 with 2 supplements
Patterns of IRs co-expression and correlations with CD4+ T-cell counts in PLWH.
(A) Overview of study design and study groups, healthy controls (HC), PLWH in early HIV-1 infection (Ei), and PLWH on fully suppressive ART (S) in S1 and S2 time points. (B) The expression of IRs …
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Figure 1—source data 1
Epidemiological and clinical data of study groups; healthy controls (HC), PLWH in early infection (Ei), and PLWH on fully suppressive ART (S) in S1 and S2 time points.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig1-data1-v1.xlsx
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Figure 1—source data 2
Frequencies of IRs expression shown in pie charts as 0 to >3 IRs expressed in CD8+ T-cell subsets and study groups.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig1-data2-v1.xlsx
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Figure 1—source data 3
Frequencies of the 32 possible combinations of expressions for TIGIT, PD-1, LAG-3, TIM-3, and CD39 in CD8+ T-cell subsets per study group.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig1-data3-v1.xlsx
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Figure 1—source data 4
Frequencies of IRs expression in total and CD8+ T-cell subsets per study group.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig1-data4-v1.xlsx
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Figure 1—source data 5
Correlations between CD4+ T-cell counts and TIGIT+, TIGIT+TIM-3+, and combinations of IRs in total and CD8+ T-cell subsets per study group.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig1-data5-v1.xlsx
Figure 1—figure supplement 1
Gating strategy for identifying total CD8+ T-cell subsets and IRs expression levels.
(A) Zebra dot plots showing the gating strategy used for the identification of total CD8+ and cellular using lineage markers (CD45RA, CCR7, and CD27) subsets as follow; naive (CD45RA+ CCR7+ CD27+), …
Figure 1—figure supplement 2
Expression profile of IRs in total and CD8+ T-cell subsets across study groups.
(A) Frequency of CD8+ T-cells and IRs expression in total CD8+ T cells across study groups (HC, Ei, S1 and S2) (B) Frequency of IRs expression in CD8+ T-cell subsets. Scatter plots represent median …
Figure 2
Unsupervised net-SNE analyses of total CD8+ T-cells.
(A) Gating strategy for selecting total CD8+ T-cells (top), net-SNE plots of HC, Ei, S1, S2 and all merge groups. (B) Representative net-SNE visualization of surface markers. The colour gradient …
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Figure 2—source data 1
Unsupervised net-SNE analyses of total CD8+ T-cells.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig2-data1-v1.xlsx
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Figure 2—source data 2
Cluster cell frequencies from net-SNE analyses in total CD8+ T-cells per study group.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig2-data2-v1.xlsx
Figure 3 with 1 supplement
Unsupervised net-SNE analyses of SEB-activated CD8+ T-cells.
(A) Gating representation of CD107a, IFNγ and IL-2 expression in HIV-1-specific CD8+ T-cells (top), net-SNE plots of HC, Ei, S1, S2 and merge groups of SEB-activated CD8+ T-cells (bottom). (B) …
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Figure 3—source data 1
Unsupervised net-SNE analyses of SEB-activated CD8+ T-cells.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig3-data1-v1.xlsx
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Figure 3—source data 2
Cluster cell frequencies from net-SNE analyses of SEB-activated CD8+ T-cells per study group.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig3-data2-v1.xlsx
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Figure 3—source data 3
Supervised analyses of CD107a, IFNγ and IL-2 frequencies of SEB-activated CD8+ T-cells per study groups.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig3-data3-v1.xlsx
Figure 3—figure supplement 1
Supervised analyses of SEB-activated CD8+ T-cells.
(A) The total frequency of CD107a, IFNγ and IL-2 SEB-activated CD8+ T-cells in HC, Ei, S1, and S2. Data represent median and interquartile ranges. (B) Table of median frequencies of CD107a, IFNγ and …
Figure 4 with 1 supplement
Unsupervised and supervised analyses of HIV-1-specific CD8+ T-cells.
(A) Gating representation of CD107a, IFNγ, and IL-2 expression in HIV-1-specific CD8+ T-cells (top), net-SNE plots of Ei, S1, S2 and merge groups for HIV-1-specific CD8+ T-cells (bottom). (B) …
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Figure 4—source data 1
Unsupervised net-SNE analyses of HIV-1-specific CD8+ T-cells.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig4-data1-v1.xlsx
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Figure 4—source data 2
Cluster cell frequencies from net-SNE analyses of HIV-1-specific CD8+ Tcells per Ei and S (S1–S2) study groups.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig4-data2-v1.xlsx
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Figure 4—source data 3
Supervised analyses of CD107a, IFNγ and IL-2 frequencies of HIV-1-specific CD8+ T-cells in Ei and S (S1–S2) study groups.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig4-data3-v1.xlsx
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Figure 4—source data 4
Frequencies of CD107a, IFNγ, and IL-2 expression in TIGIT+ and TIGIT+ TIM-3+HIV-1-specific memory CD8+ T-cell subsets in Ei and S (S1–S2) study groups.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig4-data4-v1.xlsx
Figure 4—figure supplement 1
Supervised analyses of HIV-1-specific CD8+ T-cell responses.
(A) Frequency of CD107a, IFNγ and IL-2 HIV-1-specific CD8+ T-cells in Ei, S1 and S2. Data represent median and interquartile ranges. (B) Table of median frequencies of CD107a, IFNγ and IL-2 …
Figure 5
Effect of TIGIT, TIM-3, and TIGIT +TIM-3 mAb blockade in HIV-1-specific CD8+ T-cell responses in PLWH on ART.
(A) Representative flow cytometry plots gated on CD8+ T-cells, in the absence of HIV-1 Gag stimulation (basal condition) and presence of HIV-1 Gag stimulation with isotype control, αTIGIT, αTIM-3, …
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Figure 5—source data 1
Unsupervised net-SNE analyses for HIV-1-specific CD8+ T-cells in PLWH on ART.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig5-data1-v1.xlsx
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Figure 5—source data 2
Frequencies of CD107a, IFNγ, and IL-2 expression in total and subsets of HIV-1-specific CD8+ T-cells in PLWH on ART.
- https://cdn.elifesciences.org/articles/83737/elife-83737-fig5-data2-v1.xlsx
Author response image 1
Graphs represent paired comparisons of the frequency of live cells in PBMC samples in short-term ICB studies.
A. Graphs indicate the percentage of live cells in HIV-1 condition (Gag peptide pool) compared to HIV-1 + IgG2 isotype, HIV-1 + IgG1 isotype and HIV-1 + IgG2a+IgG1. B. Graphs indicate the % of live …
Additional files
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Supplementary file 1
The epidemiological and clinical characteristics of the study groups.
- https://cdn.elifesciences.org/articles/83737/elife-83737-supp1-v1.docx
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MDAR checklist
- https://cdn.elifesciences.org/articles/83737/elife-83737-mdarchecklist1-v1.pdf
