Author, as appears in the article.: Collins DR; Urbach JM; Racenet ZJ; Arshad U; Power KA; Newman RM; Mylvaganam GH; Ly NL; Lian X; Rull A; Rassadkina Y; Yanez AG; Peluso MJ; Deeks SG; Vidal F; Lichterfeld M; Yu XG; Gaiha GD; Allen TM; Walker BD

Department: Medicina i Cirurgia Bioquímica i Biotecnologia

URV's Author/s: RULL AIXA, ANNA / Vidal Marsal, Francisco

Keywords: activation ex-vivo exhaustion expression infection pd-1 replication responses sequence alignment Cd8 t cell dysfunction + Cd8(+) t-cells Hiv control Human immunology

Abstract: Spontaneous control of HIV infection has been repeatedly linked to antiviral CD8+ T cells but is not always permanent. To address mechanisms of durable and aborted control of viremia, we evaluated immunologic and virologic parameters longitudinally among 34 HIV-infected subjects with differential outcomes. Despite sustained recognition of autologous virus, HIV-specific proliferative and cytolytic T cell effector functions became selectively and intrinsically impaired prior to aborted control. Longitudinal transcriptomic profiling of functionally impaired HIV-specific CD8+ T cells revealed altered expression of genes related to activation, cytokine-mediated signaling, and cell cycle regulation, including increased expression of the antiproliferative transcription factor KLF2 but not of genes associated with canonical exhaustion. Lymphoid HIV-specific CD8+ T cells also exhibited poor functionality during aborted control relative to durable control. Our results identify selective functional impairment of HIV-specific CD8+ T cells as prognostic of impending aborted HIV control, with implications for clinical monitoring and immunotherapeutic strategies.

Thematic Areas: Ciências biológicas i Ciências biológicas ii Ciências biológicas iii Farmacia General medicine Immunology Immunology and allergy Infectious diseases Medicina i Medicina ii

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: francesc.vidal@urv.cat

Author identifier: 0000-0002-6692-6186

Record's date: 2023-02-19

Papper version: info:eu-repo/semantics/acceptedVersion

Link to the original source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00337-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS107476132100337X%3Fshowall%3Dtrue#%20

Papper original source: Immunity. 54 (10): 2372-2384.e7

APA: Collins DR; Urbach JM; Racenet ZJ; Arshad U; Power KA; Newman RM; Mylvaganam GH; Ly NL; Lian X; Rull A; Rassadkina Y; Yanez AG; Peluso MJ; Deeks SG; V (2021). Functional impairment of HIV-specific CD8+ T cells precedes aborted spontaneous control of viremia. Immunity, 54(10), 2372-2384.e7. DOI: 10.1016/j.immuni.2021.08.007

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Article's DOI: 10.1016/j.immuni.2021.08.007

Entity: Universitat Rovira i Virgili

Journal publication year: 2021

Publication Type: Journal Publications