Extended Data Figure 5. SIV-specific CD8⁺ T-cells display an exhausted phenotype that is not rescued by ICB during suppressive ART, but by viral rebound following ATI.

Within memory CD8⁺ T-cells at the on-ART, pre-treatment baseline (d-29 p.t.; n=5 ICB-treated, Mamu-A*01⁺ RMs) the frequencies of exhaustion, proliferative and activation biomarkers (as indicated above) were quantified via flow cytometry in SIV-specific and non-specific subsets, as assessed by anti-Gag-CM9 staining (as indicated below) in (a) LN and (b) PBMCs. Likewise, within LN SIV-specific memory CD8⁺ T-cells the frequencies of (c) Ki-67⁺, (d) HLA-DR⁺CD38⁺, (e) T-bet⁺, and (f) Granzyme B⁺ cells were measured at the pre-ICB baseline and following the fourth ICB infusion (d28 p.t.). Likewise, the frequencies of (g) Ki-67⁺, (h) HLA-DR⁺CD38⁺, (i) T-bet⁺, and (j) Granzyme B⁺ cells within SIV-specific memory CD8⁺ T-cells in PBMCs were quantified at the pre-ICB baseline, following the third ICB treatment (d21 p.t.), and 15 days following ART interruption (d50 p.t.). Analyses were conducted in up to 6 Mamu-A*01⁺ RMs (g,h,i,j), of which 5 were ICB-treated (a,b,c,d,e,f). Each data point represents an individual animal, as indicated by shape, and those with ICB-related viral reactivation in plasma are represented as closed data points. Averaged data are presented as the mean ± SEM and were analyzed with (a,b) a one-way, pair-wise ANOVA using a Bonferroni correction for multiple corrections.