Kinetics of cytokine secretion by HIV-1–specific CD8 T cells present a unique pattern in controllers. (A-C) Secretion of cytokines was determined in supernatants of PBMCs 6, 24, and 72 hours after stimulation with HLA-I-–matched panels of optimal HIV-1 epitopes (discovery cohort, n = 64 subjects); comparative kinetics analysis of mean IFN-γ (A), IL-2 (B), and TNF-α (C) secretion in the 3 clinical cohorts after a single antigenic encounter. HC indicates HIV-1 controllers; CP, chronic progressors; and ARTC, ART-treated subjects. (D-E) CFSE-labeled PBMCs were incubated with optimal HIV-1 CD8 T-cell epitopes and ICS and CFSE intensity were measured in CD8 T cells at 6, 24, 72, 96, and 168 hours after stimulation. Control (no antigen) conditions show minimal background (data not shown. (D) Representative examples of responses of high magnitude in an elite controller (upper row) and a chronic progressor (lower row). (E) Summary data of the kinetics of IFN-γ secretion over a 7-day period after a single antigenic encounter for immunodominant responses in 3 HC subjects (blue line) and 3 CP subjects (red line). Mean cytokine responses for each subject was calculated at each time point (6, 24, and 72 hours). Vertical interval bars correspond to the SEM.