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Rüeger, S.* ; Gruener, E.* ; Wang, D.* ; Abdool, F.S.* ; Ober, V.* ; Vallée, T.* ; Stirner, R.* ; Conca, R.* ; Andrä, I.* ; Rogers, L.* ; Zahn, R.* ; Gersbacher, E.* ; Eger, J.* ; Pauli, R.* ; Postel, N.* ; Spinner, C.D.* ; Vehreschild, J.J.* ; Stecher, M.* ; Nitschko, H.* ; Eberle, J.* ; Bogner, J.R.* ; Seybold, U.* ; Draenert, R.* ; Leslie, A.* ; Kløverpris, H.N.* ; Geldmacher, C.* ; Muenchhoff, M.* ; Held, K. ; Roider, J.*

Early treatment and PD1 inhibition enhance HIV-specific functionality of follicular CD8+ T cells.

JCI insight 10:e180309 (2025)

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	Open Access Gold

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People living with HIV treated during acute infection are the group for whom achieving functional cure appears most viable. Follicular CD8+ T cells could contribute to HIV reservoir clearance by accessing B cell follicles through CXCR5 expression. This study examines peripheral follicular CD8+ T cells using flow cytometry, transcriptome analyses, and functional assays in people treated during acute (n = 37) and chronic (n = 18) infection, as well as in individuals naturally controlling HIV (n = 20) and living without HIV (n = 10). Our results reveal that early, as opposed to late, treatment initiation preserves antiviral effector functions of follicular CD8+ T cells, which are further enhanced by PD1 inhibition. We also identify a correlation between follicular CD8+ T cells and intact proviral HIV DNA levels in acute, but not chronic, infection. Longitudinal transcriptomic analysis of peripheral effector cells after 48 weeks of suppressive therapy indicated traits of recent antigen exposure, suggesting potential recirculation into lymphoid tissue. These findings underscore the pivotal role of follicular CD8+ T cells in anti-HIV responses and support investigating targeted cure strategies, such as anti-PD1 therapy, especially in individuals initiating treatment during acute infection.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Aids/hiv ; Adaptive Immunity ; Immunology ; T Cells; Cd8(+) T-cells; Immunodeficiency Virus-infection; Immune Checkpoint Blockade; Lymphocyte Response; Down-regulation; Plasma Viremia; Siv Viremia; Rna-seq; Ex-vivo; In-vivo

ISSN (print) / ISBN 2379-3708

e-ISSN 2379-3708

Journal JCI insight

Quellenangaben Volume: 10, Issue: 7, Article Number: e180309

Publisher Clarivate

Publishing Place Ann Arbor, Michigan

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Global Health (UGH)

Grants Wellcome Trust
Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) - Science for Africa Foundation
NIH
German Federal Ministry of Education and Research (BMBF) through DZIF
Bavarian Gender Equality Grant
Else Kroner-Fresenius-Stiftung (EKFS)
UK Foreign, Commonwealth & Development Office
European Union

Gilead Sciences Inc.
Bill & Melinda Gates Foundation
DZIF