Enhanced functionality in nonprogressors is not due to the presence of HLA-B57 or maintenance of central memory cells. (A) CMV-, EBV-, and influenzaspecific CD8⁺ T cells in the progressors are not restricted in functionality either off (left) or after initiation of ART (right). Each pie chart represents the average CD8⁺ T-cell response from a group of 5 progressors either prior to or after initiation of HAART. The colors correspond to the number of functions expressed, as shown. (B) HLA-B57⁺ (n = 6) and B57^– (n = 3) nonprogressors were separated (left 2 pie charts), and the functionality of their HIV Gag-specific CD8⁺ T-cell responses compared with each other, and to HLA-B57⁺ (n = 6) and B57^– (n = 6) progressors (right 2 pie charts). The colors in each pie chart correspond to the number of functions depicted by colored squares. (C) 5+ and (D) 4+ IL-2^– responding cells can have varied memory phenotype. Twelve-color flow cytometry was performed to characterize the memory phenotype of responding CD8⁺ T cells. Plots depict CD8⁺ T cells responding with either the 5+ (red contours) or 4+IL-2^– (orange contours) functional profile overlaid onto a density plot of the memory phenotype, as determined by CD27 and CD45RO, of the total CD8⁺ T-cell population. Inset in each plot is a histogram representing CD57 expression in the responding cells. (E) Initiation of ART does not improve CD8⁺ T-cell functionality in most individuals. Plots show the proportion of the total response against the indicated HIV peptide mix (indicated at top of each plot together with stimulus) prior to (OFF) and 6 to 12 months after (ON) initiation of ART. Each subject is represented by a colored line/symbol, and the symbols indicate the particular stimuli tested. The black box represents the mean response on or off therapy, with the SD of the mean shown as a black bar.