TY - JOUR

T1 - Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype

AU - Vieira, Vinicius

AU - Lim, Nicholas

AU - Singh, Alveera

AU - Leitman, Ellen

AU - Dsouza, Reena

AU - Adland, Emily

AU - Muenchhoff, Maximilian

AU - Roider, Julia

AU - Lopez, Miguel Marin

AU - Carabelli, Julieta

AU - Giandhari, Jennifer

AU - Groll, Andreas

AU - Jooste, Pieter

AU - Prado, Julia G.

AU - Thobakgale, Christina

AU - Dong, Krista

AU - Kiepiela, Photini

AU - Prendergast, Andrew J.

AU - Tudor-Williams, Gareth

AU - Frater, John

AU - Walker, Bruce D.

AU - Ndung'U, Thumbi

AU - Ramsuran, Veron

AU - Leslie, Alasdair

AU - Kløverpris, Henrik N.

AU - Goulder, Philip

N1 - Publisher Copyright: © 2023, Vieira et al.

PY - 2023

Y1 - 2023

N2 - HIV nonprogression despite persistent viremia is rare among adults who are naive to antiretroviral therapy (ART) but relatively common among ART-naive children. Previous studies indicate that ARTnaive pediatric slow progressors (PSPs) adopt immune evasion strategies similar to those described in natural hosts of SIV. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T cells immediately before ATI was the main predictor of slow progression during ATI. PD-1+CD8+ T cell frequency was also negatively correlated with CCR5 and HLA-DR expression on CD4+ T cells and predicted stronger HIV-specific T lymphocyte responses. In the CD8+ T cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas pediatric progressors and viremic adults had a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T cells was associated with higher proliferative activity and stronger Gag-specific effector functionality. These data prompted the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in infants who received early ART with a preserved and nonexhausted T cell compartment.

AB - HIV nonprogression despite persistent viremia is rare among adults who are naive to antiretroviral therapy (ART) but relatively common among ART-naive children. Previous studies indicate that ARTnaive pediatric slow progressors (PSPs) adopt immune evasion strategies similar to those described in natural hosts of SIV. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T cells immediately before ATI was the main predictor of slow progression during ATI. PD-1+CD8+ T cell frequency was also negatively correlated with CCR5 and HLA-DR expression on CD4+ T cells and predicted stronger HIV-specific T lymphocyte responses. In the CD8+ T cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas pediatric progressors and viremic adults had a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T cells was associated with higher proliferative activity and stronger Gag-specific effector functionality. These data prompted the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in infants who received early ART with a preserved and nonexhausted T cell compartment.

U2 - 10.1172/jci.insight.156049

DO - 10.1172/jci.insight.156049

M3 - Journal article

C2 - 36602861

AN - SCOPUS:85147720718

VL - 8

JO - JCI Insight

JF - JCI Insight

SN - 2379-3708

IS - 3

M1 - e156049

ER -