SIV-specific CD8⁺ T cells from LTNP/EC mediate greater lysis of SIV-infected CD4⁺ T-cell targets compared with progressors.

<p>GrB target cell activity (<b>A</b>) and infected CD4 elimination (ICE) (<b>B</b>) are shown for LTNP/EC (n = 10, GrB target cell activity; n = 11, ICE) and progressors (n = 11). Horizontal bars represent the median values. <b>C.</b> Correlation between ICE and GrB target cell activity (n = 22) was determined by the Spearman rank method. Red, blue and cyan dots represent LTNP/EC, progressors and one SIV-uninfected animal, respectively.</p

Infected CD4 Elimination (ICE) inversely correlates with plasma SIV RNA levels in SIV-infected rhesus macaques.

<p>Red dots represent LTNP/EC (n = 11). Blue dots represent progressors (n = 11). Statistical analysis was performed by the Spearman rank method.</p

SIV-specific CD8⁺ T cell cytotoxicity measured by granzyme B delivery or Infected CD4 Elimination (ICE).

<p><b>A.</b> The top panels show granzyme B (GrB) target cell activity representative of a “high responder”. The bottom panels show GrB target cell activity representative of a “low responder”. Values indicate percentages of targets with increased fluorescence due to GrB substrate cleavage. Background GrB target cell activity measured in response to uninfected targets (left column) was subtracted from responses measured against infected targets (right column) to determine net GrB target cell activity (red values). <b>B.</b> ICE values calculated based on p27 expression (sum of the upper quadrants) as described in the Methods, are shown in red for the same “high responder” (78.8%, top row) and “low responder” (22.3%, bottom row) as shown in A. Quadrant values indicate percentages of gated targets. In all experiments, CD4⁺ T cell lines were used as targets. CD8⁺ T cells that had been stimulated with SIV-infected targets for 6 days were used as effectors. GrB target cell activity and ICE were calculated after 1 hour of incubation of effectors and plated at an E∶T ratio of 25∶1.</p

SIV-specific CD8⁺ T cells of LTNP/EC mediate greater per-cell killing of SIV-infected targets than those of progressors, which is not simply due to higher true E∶T ratios.

<p><b>A.</b> The true effector to target (E∶T) ratios, determined by measurements of IFN-γ-secreting CD8⁺ T-cell effectors and p27-expressing CD4⁺ T-cell targets, respectively, as described in the Methods and shown in the <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003195#ppat.1003195.s001" target="_blank">Figure S1</a> and <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003195#ppat.1003195.s002" target="_blank">Table S1</a>, were compared between LTNP/EC (n = 11) and progressors (n = 11). Horizontal bars represent the median values. <b>B, C.</b> GrB target cell activity (<b>B</b>) or ICE (<b>C</b>) responses plotted against the true E∶T ratios are shown for LTNP/EC (n = 10, GrB target cell activity; n = 11, ICE) and progressors (n = 11). GrB target cell activity is shown after subtraction of background. The response curves were analyzed by regressing ICE and GrB on log true E∶T ratios using analysis of covariance. The standard two-tailed t test from regression analysis was used to compare estimated GrB target cell activity and ICE of LTNP/EC with that of progressors at the 5.8 E∶T ratio, the median of the combined E∶T ranges of both groups.</p

Characteristics of macaques and prediction of SIV control.

<p>ICE, Infected CD4⁺ T cell Elimination (%). LTNP/EC, Long-Term Nonprogressor/Elite Controllers. SP, Slow Progressor. N/A, Not Applicable. PBMC from more than one time point were used in the animals marked with an asterisk.</p