Fig. 4.

Reduction of the Th17:Treg ratio leads to higher SIV viral loads. (A) Viral loads in infected animals from Groups A–D of Figure 3A (n=16). Macaques with high Th17:Treg ratios at the time of infection (the eight animals above the median value) are shown with dashed black lines; those with low Th17:Treg ratios (below the median) are shown with solid lines. (B) Peak viral load accurately predicts set-point viral load (p=0.0003 by linear regression, R²=0.61). (C) Viral loads observed in animals treated with IL-2 and G-CSF were higher than predicted based on Th17:Treg ratios measured before treatment. Viral loads in treated animals lie above the regression line for animals in other groups. The p value shown was calculated using a model including a dummy variable for animals receiving IL-2 and G-CSF; the coefficient for this variable was statistically significant (p=0.0002) and estimated at 0.6 log units, indicating that the intercept for a regression line appropriate to treated animals lies 0.6 log units above that for other animals. Values are plotted for six IL-2- and G-CSF-treated animals (filled markers) and 16 other animals (open markers) from Figure 3A (groups A, B, and D) and Figure 1G. The difference shown remains significant when any of these groups is removed from the analysis (p < 0.005 in all cases). (D) The Th17:Treg ratio established after treatment is correlated with the viral load that will develop after infection. Linear regression of peak viral load against the log Th17:Treg ratio, for all animals, indicates a significant trendline overall (p=0.00004). Use of a dummy variable for IL-2 and G-CSF treatment, as in Figure 4C, shows no significant difference between trendlines for treated and untreated animals (p=NS), suggesting that the Th17:Treg ratios established by treatment explain viral loads in treated animals. (E) The fraction of Th17 cells among CD4⁺ T cells correlates with viral load. Trendlines and statistical calculations are as in panel D. (F) Th17 cells in blood at the time of infection accurately predict the percentage of Th17 cells recovered from colon tissue six months later.