IL-10Rα blockade restores HIV-specific CD4 T-cell function in individuals with uncontrolled viremia. (A) CD4 T-cell proliferation was measured by flow cytometry of CFSE-labeled CD8 T cell–depleted PBMCs incubated with no antigen or HIV p24, plus isotype control antibody or IL-10Rα antibody. Numbers in upper left quadrants indicate the percentage of CD3⁺CD4⁺CFSE^low cells in each condition. Blockade of the IL-10 pathway significantly increased proliferation of p24 antigen–specific CD4 T cells, as shown in this representative sample. (B) Statistical analysis of CFSE results obtained in a cohort of 27 viremic subjects with chronic untreated infection (P < .001; Wilcoxon-matched pairs test). (C) Statistical comparison of impact of IL-10Rα blockade on HIV p24–specific CD4 T-cell proliferation in chronically HIV-infected subjects with viral loads suppressed to less than 50 RNA copies by antiretroviral therapy (ARV; n = 9), elite controllers (ELITE; n = 6), and chronically infected individuals with viral load of greater than 1000 RNA copies/mm³ (UNTREATED; n = 24) suggested a significant difference among groups (P = .001; Kruskall Wallis test, followed by Dunn posttest for paired comparisons). The vertical axis (IL-10 proliferation index) corresponds to the ratio of the fraction of proliferating (%CD3⁺CD4⁺CFSE^low) cells in the presence of the IL-10Rα blocking antibody versus isotype control. Short horizontal bars indicate median proliferation index. (D,E) Statistical analysis of data on untreated subjects in panel C (elite controllers and chronic untreated subjects) indicated a significant correlation between viral load (R = 0.5636; P < .001) in panel D, but not CD4 count (P > .05; E) with the effect of IL-10Rα blockade on HIV-specific CD4 T-cell proliferation (Spearman rank sum test).