Background
Identifying immunologic features that correlate with control of HIV/SIV after antiretroviral therapy (ART) is stopped will inform the design of improved curative strategies for HIV. Here, we characterized features of lymph node (LN) CD8+ T cells in a cohort of 10 rhesus macaques infected i.v. with SIVmac239 that achieved a range of SIV plasma viral load (pVL) set points after analytic treatment interruption (ATI; range 65-225,000 c/mL).
Methods
To identify CD8+ T cell features that correlate with subsequent post-ATI pVL set point, we performed spectral flow cytometry including SIV-specific class I tetramers on peripheral LN mononuclear cells collected pre-ATI, and at 7/8 and 15 days post-ATI (median pVL 32 and 10,600 c/mL, respectively). We also performed single cell RNA/TCR (scRNA/TCRseq) sequencing on sorted total live LN cells from a subset of animals.
Results
Prior to stopping ART, animals with low pVL set points had a higher frequency of cycling (Ki67+) CD8+ T cells within the central memory (Tcm: CD95+CD28+CCR7+), transitional memory (Ttm: CD95+CD28+CCR7-), and follicular-like (CXCR5+PD-1+) subsets (10.4% vs 6.1% p=0.01, 7.2% vs 4.7% p=0.02, and 7.5% vs 4.0% p=0.01, respectively). Low pVL set point also correlated with a higher frequency of TCF-1+ Ttm pre-ATI (Spearman’s r=-0.77, p=0.01). After treatment interruption, the frequency of Ki67+ Tcm at d7/8 post-ATI was negatively correlated with the level of SIV RNA measured in the same LN (r=-0.83, p=0.02). By scRNA/TCRseq, animals that achieved low pVL set points had a higher frequency of naïve/early memory CD4+ and CD8+ T cells post-ATI, as well as a higher frequency of an effector-like cluster of CD8+ T cells expressing CCL5, CTSW, GZMM, GZMK, and NKG7 at d7/8 post-ATI.
Conclusions
We found that animals with lower post-ATI pVL set points both start out with and then continue to maintain into early rebound a larger fraction of actively cycling CD8+ T cells in the LN
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