Disease Progression in Children With Perinatal Human Immunodeficiency Virus Correlates With Increased PD-1+ CD8 T Cells That Coexpress Multiple Immune Checkpoints

• Published in: The Journal of infectious diseases 2021-11, Vol.224 (10), p.1785-1795
• Main Authors: Tailor, Janki, Foldi, Julia, Generoso, Matthew, McCarty, Bret, Alankar, Aparna, Kilberg, Max, Mwamzuka, Mussa, Marshed, Fatma, Ahmed, Aabid, Liu, Mengling, Borkowsky, William, Unutmaz, Derya, Khaitan, Alka
• Format: Article
• Language: English
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiab204

BACKGROUNDPD-1 marks exhausted T cells, with weak effector functions. Adults living with human immunodeficiency virus (HIV) have increased levels of PD-1+ CD8 T cells that correlate with HIV disease progression, yet little is known about the role of PD-1+ CD8 T cells in children with perinatal HIV. METHODSWe enrolled 76 Kenyan children with perinatal HIV and 43 children who were HIV unexposed and quantified PD-1 levels on CD8 T cells; their coexpression with immune checkpoints (ICs) 2B4, CD160, and TIM3; correlates with immune activation and HIV disease progression; and HIV-specific and -nonspecific proliferative responses. RESULTSPD-1+ CD8 T-cell frequencies are elevated in children with perinatal HIV and associated with disease progression. The majority of PD-1+ CD8 T cells coexpress additional ICs. ART initiation lowers total PD-1 levels and coexpression of multiple ICs. The frequency of PD-1+2B4+CD160+TIM3- in PD-1+ CD8 T cells predicts weaker HIV-specific proliferative responses, suggesting that this subset is functionally exhausted. CONCLUSIONSChildren with perinatal HIV have high levels of PD-1+ CD8 T cells that are a heterogeneous population differentially coexpressing multiple ICs. Understanding the complex interplay of ICs is essential to guide the development of PD-1-directed immunotherapies for pediatric HIV remission and cure.