Figure 1. TCF-1 expression is elevated in HIV- and SIV-specific CD8⁺ T cells from controllers.

(A) Frequency of peripheral blood multimer⁺ HIV–specific CD8⁺ T cells. (B) Proliferation of HIV-specific CD8⁺ T cells in response to 6-day in vitro cognate peptide stimulation as measured by dilution of cell-trace violet (CTV). (C) Gating strategy (left: green, multimer⁺ from controller; gray, bulk CD8⁺ T cells) and distribution (right) of effector-memory phenotypes amongst multimer⁺ cells (TN, naive [gate includes, and likely primarily contains, CD95⁺ stem-cell memory cells, TSCM]; TCM, central memory; TTM, transitional memory; TEM, effector memory; TEMRA, effector memory-RA, separated by level of CD27 expression). (D) Gating (top left; TCF-1⁺ population gated based on CD8⁺ TN population from an HIV-uninfected participant, blue), representative flow plots (top right; median [range]), and summary data (bottom) showing TCF-1 expression in multimer⁺ HIV–specific CD8⁺ T cells from viremic (VIR; magenta), ART-suppressed (ARTs; black), and controller (C; green) individuals of all multimer specificities (left) and within the HIV Gag/HLA-A*02:SL9 multimer⁺ population (right). (E) TCF-1 expression in the SIV Gag/Mamu-A*01:CM9 multimer⁺ population from viremic and controller macaques. Phenotypes assessed by flow cytometry. FMO, fluorescence-minus-1 control. Box plots: median ± IQR. The human studies included data from a maximum of n = 13 viremic, 10 ART-suppressed, and 12 controller participants (as indicated in each figure), some with 2 multimer specificities. The macaque studies included n = 6 viremic and 4 controller animals. Linear mixed effects models to account for clustering within participants (A, C, D), Kruskal-Wallis followed by Dunn’s multiple comparison testing (B), Wilcoxon’s rank sum (E) were used.