Stimulation with a low antigen concentration induces the CD38⁻/HLA-DR⁺ phenotype on specific CD8⁺ T cells.

<p>(A) Graphs representing the frequency of (A) CD38⁻/HLA-DR⁺ cells (dark histograms) and (B) CD38⁺/HLA-DR⁺ cells (dark gray histograms) among activated EBV-specific healthy donor CD8⁺ T cells (i.e. those expressing CD38 and/or HLA-DR) after a four-day culture period (n = 8).</p

CD38 and HLA-DR expression on bulk and HIV-specific CD8⁺ T cells.

<p>(A) Proportions of bulk CD8⁺ T cells from HD (n = 16, light gray bars), HAART-treated patients (n = 19, mid gray bars), viremic patients (n = 21, dark gray bars) and HIC (n = 79, black bars) expressing CD38 and HLA-DR. (C) Proportions of HIV-specific CD8⁺ T cells from HAART-treated patients (n = 13, mid gray bars), viremic patients (n = 39, dark gray bars) and HIC (n = 80, black bars) expressing CD38 and HLA-DR. Pie charts representing CD38⁻/HLA-DR⁻ (white), CD38⁻/HLA-DR⁺ (black), CD38⁺/HLA-DR⁻ (light gray) and CD38⁺/HLA-DR⁺ (dark gray) cells among bulk (B) and HIV-specific CD8⁺ T cells (D). Statistical differences shown in the pie charts are based on the difference in the frequency of the CD38⁻/HLA-DR⁺ subset between the different groups. * <i>P</i><0.05, ** <i>P</i><0.01, *** <i>P</i><0.001.</p

Study population.

<p>Median values [1^st–3^rd interquartile range] are shown for age, time since diagnosis, CD4⁺ and CD8⁺ T cell counts, and HIV RNA viral loads.</p>a<p>Viremic and HAART-treated patients' RNA viral loads were measured using an assay with a quantification limit of <50 copies/ml, while values in HIC were obtained with ultrasensitive assays.</p

High antigen sensitivity is associated with a high frequency of CD38⁻/HLA-DR⁺ cells in HIC.

<p>The antigen sensitivity of HIV-specific CD8⁺ T cells was measured in ELISpot assays with serial limiting dilutions of antigenic peptides (from 10⁻⁵ to 10⁻¹¹ M) and was expressed as the log molar concentration of peptide yielding 50% of the maximum response (EC_50%). Correlations between the proportion of CD38⁻/HLA-DR⁺ (A) or CD38⁺/HLA-DR⁺ (B) and the antigen sensitivity of HIV-specific CD8⁺ T cells from HIC. Correlations were evaluated using the Spearman rank correlation coefficient. The Spearman r correlation and the Pearson correlation curve are indicated for significant correlations (n = 47).</p

Influence of stimulatory conditions on the activation phenotype of specific CD8⁺ T cells.

<p>(A) Representative dot plots of HLA-DR and CD38 expression in unstimulated conditions (upper graph), after IFN-α stimulation (middle graph) or peptide stimulation (2 µM, lower graph) among specific (dark dots) and non-specific (gray dots) CD8⁺ T cells from healthy donors after a four-day culture period. CD38 and HLA-DR expression on bulk (C left panel) and specific CD8⁺ T cells (B and C right panel). (B) Flow cytometry histograms showing representative results for cells from one individual in unstimulated conditions (dark lines), after IFN-α stimulation (light gray histograms) or peptide stimulation (dark gray histograms). (C) Surface expression of CD38 (white bars) and HLA-DR (gray bars) on bulk and specific CD8⁺ T cells (n = 4).</p

Qualitative features of CD38⁻/HLA-DR⁺ and CD38⁺/HLA-DR⁺ HIV-specific CD8⁺ T cell subsets in HIC.

<p>(A) Bcl-2 expression on CD38⁻/HLA-DR⁺ and CD38⁺/HLA-DR⁺ HIV-specific CD8⁺ T cells (n = 11). (B) Proportion of CD38⁻/HLA-DR⁺ and CD38⁺/HLA-DR⁺ HIV-specific CD8⁺ T cells producing both IFN-γ and IL-2 among HIV-specific CD8⁺ T cells producing IFN-γ or IL-2 (n = 35). (C) Fold increase in CD38⁻/HLA-DR⁺ and CD38⁺/HLA-DR⁺ HIV-specific CD8⁺ T cell numbers after 5 days of culture with HIV peptides (2 µM) (n = 7). (D–E) Proportion of CD38⁻/HLA-DR⁺ and CD38⁺/HLA-DR⁺ HIV-specific CD8⁺ T cells producing perforin (D) and granzyme B (E) (n = 35). (F) Graphs representing percentage cytotoxicity (measured as granzyme-B-mediated intracellular cleavage of a fluorogenic substrate) of CD38⁻/HLA-DR⁺ and CD38⁺/HLA-DR⁺ HIV-specific CD8⁺ T cells (n = 11). * <i>P</i><0.05, ** <i>P</i><0.01, *** <i>P</i><0.001.</p

Characteristics at baseline and at cART initiation in 34 elite Controllers (ECs) and 478 chronically viremic (VIRs) patients from the ANRS COPANA Cohort.

<p>Data are median [IQR] or n (%);</p><p>According to own cohort’s definitions of ECs;</p><p>SSA/Car/BA = Sub-Saharan African, Caribbean or African-American origin.</p

Estimated CD4 cell count dynamics in viremic patients (VIRs: n = 478) and elite controllers (ECs: n = 34) in mixed-effect linear models (mean CD4 T cells gain after 12 months of cART was significantly lower in ECs than in VIRs (p = 0.048)).

<p>Estimated CD4 cell count dynamics in viremic patients (VIRs: n = 478) and elite controllers (ECs: n = 34) in mixed-effect linear models (mean CD4 T cells gain after 12 months of cART was significantly lower in ECs than in VIRs (p = 0.048)).</p