Early treatment and PD1 inhibition enhance HIV-specific functionality of follicular CD8+ T cells
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.
Authors
- R. Zahn (ORCID: https://orcid.org/0000-0001-6362-1507)
- Elke Gersbacher
- Raffaele Conca (ORCID: https://orcid.org/0000-0003-0683-5474)
- Ulrich Seybold (ORCID: https://orcid.org/0000-0001-9830-8350)
- Renate Stirner
- Johannes Richard Bogner (ORCID: https://orcid.org/0000-0001-8628-1533)
- Rika Draenert (ORCID: https://orcid.org/0000-0001-6049-3626)
- Lisa M. Rogers (ORCID: https://orcid.org/0000-0002-3516-5812)
- Christof Geldmacher (ORCID: https://orcid.org/0000-0001-6777-7621)
- Christoph D. Spinner (ORCID: https://orcid.org/0000-0002-3875-5367)
- Melanie Stecher (ORCID: https://orcid.org/0000-0002-3460-1299)
- Sina Rüeger (ORCID: https://orcid.org/0000-0003-2848-9242)
- Maria J. G. T. Vehreschild (ORCID: https://orcid.org/0000-0003-0446-3224)
- Kathrin Held (ORCID: https://orcid.org/0000-0001-7057-6935)
- Immanuel Andrä (ORCID: https://orcid.org/0000-0003-1543-9158)
- Veronica Ober (ORCID: https://orcid.org/0000-0001-8631-9255)
- Ramona Pauli
- Hans Nitschko
- Maximilian Muenchhoff (ORCID: https://orcid.org/0000-0001-7016-0470)
- Josef Eberle (ORCID: https://orcid.org/0000-0001-6770-0309)
- Julia Roider (ORCID: https://orcid.org/0000-0002-1347-2838)
- Theresa La Vallee
- Nils Postel
- Henrik N. Kløverpris (ORCID: https://orcid.org/0000-0002-2165-3313)
- Danni Wang (ORCID: https://orcid.org/0009-0008-1471-5070)
- Joanna Eger
- Al Leslie
- Eva Gruener
- Faiaz Shaik Abdool
Institutions
- Goethe University Frankfurt (DE)
- University of Copenhagen (DK)
- University of Cologne (DE)
- Helmholtz Zentrum München (DE)
- LMU Klinikum (DE)
- Fraunhofer Institute for Translational Medicine and Pharmacology (DE)
- Laboratoire National de Référence (MA)
- German Center for Infection Research (DE)
- Medizinisches Versorgungszentrum Prof. Mathey, Prof. Schofer (DE)
- Medical Genetics Center (DE)
- MUC Research (Germany) (DE)
- München Klinik (DE)
- Africa Health Research Institute (ZA)
- University Hospital Frankfurt (DE)
- Institute of Medical Microbiology and Hygiene (DE)
- University Hospital Cologne (DE)
- Institute of Infection and Immunity (CA)
- University College London (GB)
- Technical University of Munich (DE)
- Ludwig-Maximilians-Universität München (DE)
- University of KwaZulu-Natal (ZA)
Publication Details
- Journal
- JCI Insight
- Published
- 2025-04-07
- DOI
- https://doi.org/10.1172/jci.insight.180309
- Citations
- 4
- Primary Topic
- HIV Research and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 4.15
Funders
- Bill and Melinda Gates Foundation
- Gilead Sciences
- Deutsches Zentrum für Infektionsforschung
- Wellcome Trust
- European Commission
- Bundesministerium für Bildung und Forschung
- Else Kröner-Fresenius-Stiftung
- National Institutes of Health