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, in cells from HIC WR are in orange, genes upregulated in cells from HIC WR are in red
, A) Percentage of cells carrying high levels of GrZB (left) and expression levels (median fluorescence 1039 intensity, MFI) of HIF1? among HIV-specific CD8+ T CM cells from HIC (n=10 individuals) and cART 1040 (n=7 individuals) as determined by flow cytometry. B) Flow cytometry analyses of fatty acid (BODIPY) 1041 and glucose (NBDG) uptake by central memory CD8+ T cells from cART, p.1042
, Results are expressed as the relative MFI 1043 compared to the MFI (set as 100) obtained with reference cells from a non-infected donor, which 1044 were analyzed in parallel for each experiment. The ratio of fatty acid vs glucose uptake for each 1045 individuals is also shown (right panel). (A,B) A non-parametric two-tailed Mann-Whitney test was 1046 used to compare differences between the groups. Each symbol represents values for cells from one 1047 individual
, CD107a and IL2 production) by HIV-1051 specific CD8+ T cells from HIV controllers (n=11 individuals, red symbols) and cART (n=8 individuals, 1052 blue symbols, [two individuals, 670115 and 350108, did not show TNFa responses above background 1053 in any conditions]) against a pool of HIV-Gag peptides in control medium, in medium without glucose 1054 and in the presence of menadione. The ratio, production and total response (sum of TNF?, IFN?
, Polyfunctional responses (3 or 4 functions; i.e. co-1057 expression of TNF?, IFN?, CD107a, or IL2) against a pool of HIV-Gag peptides by HIV-specific CD8+ T 1058 cells from HIV controllers (n=11 individuals, red symbols) and cART individuals (n=9 individuals, blue 1059 symbols, excluding 670115 with no Total HIV response) in control medium, in medium without glucose, and in the presence of menadione. (a,b) Each symbol represents values for cells from one 1061 individual. Medians are represented as horizontal lines. A non-parametric two-tailed Wilcoxon 1062 paired test was used to compare HIV-specific CD8+ T-cell responses in different conditions to the 1063 control condition. (c) Donut plots representing the relative magnitude (represented by the size) 1064 compared to control condition and polyfunctionality (Blue: 1 function; red: 2 functions; green: 3 1065 functions; yellow: 4 functions) of HIV-specific CD8+ T cells from HIV controllers (n=11 individuals) and 1066 cART individuals (n=9 individuals, HIV-specific CD8+ T cell TNF? responses in medium without and with glucose, for HIC controllers (red 1056 symbols) and cART individuals (blue symbols), (b)
, R&D). b) Oxygen consumption rates (two representative examples, means and standard 1073 deviation [n=3 replicates] at each time point are shown for each analysis, left), basal glycolysis and 1074 basal and maximal respiratory capacity (right, cells from n=8 individuals) by CD8+ T cells from cART-1075 individuals pre-incubated or not with IL-15. Arrows indicate the time of addition of Oligomycin, FCCP 1076 and Rotenone/antimycin. c) TNF? production by HIV-and CMV-specific CD8+ T cells from cART (n=8 1077 individuals) upon stimulation with pools of HIV-Gag (left) and CMVp665 peptides (right) in control 1078 medium. Cells had been pre-incubated (overnight) or not with IL-15. d) Representative example (left) 1079 and summary (cells from n=10 individuals) of viral suppression assays showing the capacity of CD8+ T 1080 cells from cART, acid (BODIPY) uptake (MFI) by central memory CD8+ T cells from cART individuals (blue 1071 circles, n=7 individuals) after 48-72h incubation in the absence (control) or in presence of IL-15 1072
, Data are means (and standard deviation for bar plots) of three replicates. (a-d) Each 1082 symbol represents values for cells from one individual. Medians are represented as horizontal lines. A 1083 non-parametric two-tailed Wilcoxon paired test was used to compare HIV-specific CD8+ T-cell 1084