Hiv-1 Controllers Possess a Unique CD8+ T Cell Activation Phenotype and Loss of Control Is Associated With Increased Expression of Exhaustion Markers

Authors

Amber D. Jones
Zachary Capriotti
Erin Santos
Angel Lin
Rachel Van Duyne
Stephen Smith
Zachary Klase

Document Type

Article

Presentation Date

8-28-2025

Comments

This article is the author's final published version in PLoS One, Volume 20, Issue 8, August 2025, Article Number e0328706.

The published version is available at https://doi.org/10.1371/journal.pone.0328706. Copyright © 2025 Jones et al.

Abstract

BACKGROUND: HIV-1 controllers are a rare population of individuals that exhibit spontaneous control of HIV-1 infection without antiretroviral therapy. Understanding the mechanisms by which HIV-1 controllers maintain and eventually lose this ability would be highly valuable in HIV-1 cure or vaccine research. Previous work revealed the ability of CD8+ T cells isolated from HIV-1 controllers to suppress HIV-1 replication in matched CD4+ T cells and PBMCs ex vivo and suggested the loss of control may be tied to CD8+ T cell exhaustion.

RESULTS: We explored whether CD8+ T cell exhaustion plays a role in the maintenance and loss of control by examining immune characteristics of HIV-1 persistent controllers and transient controllers who lost control within the duration of the study. Using flow cytometry, we analyzed exhaustion marker expression on CD8+ T cells from HIV-1 controllers and determined that they maintain a unique exhaustion profile as compared to people without HIV-1 and HIV-1 standard progressors. The low level of T cell exhaustion seen in HIV-1 controllers was reversed when these individuals lost control and showed increased viral loads. Combinatorial immune checkpoint blockade targeting exhaustion markers was able to restore ex vivo control in CD8+ T cells from former controllers.

CONCLUSIONS: These results suggest that CD8+ T cell exhaustion compromises the ability to control viral replication in HIV-1 controllers. The character of exhaustion in response to HIV-1 and therapy is distinct in HIV-1 persistent controllers, transient controllers and standard progressors.

Recommended Citation

Jones, Amber D.; Capriotti, Zachary; Santos, Erin; Lin, Angel; Van Duyne, Rachel; Smith, Stephen; and Klase, Zachary, "Hiv-1 Controllers Possess a Unique CD8+ T Cell Activation Phenotype and Loss of Control Is Associated With Increased Expression of Exhaustion Markers" (2025). Kimmel Cancer Center Papers, Presentations, and Grand Rounds. Paper 82.
https://jdc.jefferson.edu/kimmelgrandrounds/82

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Language

English