2026-04-19T13:35:13Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/2236612025-11-19T22:46:06Zcom_2072_1057col_2072_478916col_2072_478917

Unveiling altered CD8 T-cell metabolism and homeostatic proliferation behind a low CD4/CD8 ratio in ART-suppressed HIV individuals with normal CD4 recovery Garrido Rodríguez, Vanesa Bulnes Ramos, Ángel Olivas Martínez, Israel Mar Pozo Balado, María del Tejerina-Picado, Francisco Gutiérrez, Félix Marco Sánchez, Cristina Tiraboschi, Juan Manuel Castillo Navarro, Antonia Bernal, Enrique García Guerrero, María C. Puertas Castro, Ma. Carmen Peraire, Joaquim Rull, Anna Martínez Picado, Francisco Javier Pacheco, Yolanda María CoRIS cohort Cèl·lules T Immunopatologia VIH (Virus) T cells Immunopathology HIV (Viruses) Background: People living with chronic HIV (PLWH) show immune dysfunction, despite viral suppression and normal CD4 recovery, particularly those with low CD4/CD8 ratios. Subjacent cellular alterations of such a reliable marker of clinical progression remain elusive. Methods: Categorization by CD4/CD8 ratio after three year of therapy (R < 0.8/R > 1.2, n = 28/n = 24) and post-hoc reclassification by nadir-CD4 (N <= 350/N > 350) were performed in PLWH achieving viral suppression and CD4 >= 500. CD4 T cell-associated viral reservoir, as well as metabolism-related gene expression, glucose uptake ability, relative telomere length (RTL), and thymic output for CD4 and CD8 T cells, were determined. Results: Patients with a CD4/CD8 ratio < 0.8 exhibited reduced CD8 T-cell glucose uptake ability after stimulation (p = 0.007) and trends to shorter RTL (p = 0.093) and to larger CD4-associated viral reservoir (p = 0.068) than R > 1.2. Differently, patients with nadir <= 350 exhibited altered CD4 and CD8 T-cell expression of metabolism-related genes, although no differences in glucose uptake ability, and shorter RTL in both cell subsets, but similar viral reservoir to patients with nadir >350. Remarkably, viral reservoir and both CD4 and CD8 thymic output showed inverse associations (r = -0.623, p = 0.01 and r = -0.661, p = 0.038, respectively). Conclusion: A low CD4/CD8 ratio in chronic PLWH stands on a larger viral reservoir in CD4 T cells and metabolic alterations in CD8 T cells, probably related to its exhaustion and compromised effector functionality, and thymic output could contribute to such alterations. Patients with lower nadir-CD4 showed a resting-like CD4 phenotype and a metabolically active CD8 subset, without further viral reservoir extension. Persistence of low CD4/CD8 ratio and low nadir-CD4 counts seems to rely on different immune damage. 2025-11-19T22:46:05Z 2025-11-19T22:46:05Z 2025-10-15T07:16:51Z 2025-10-15T07:16:51Z 2025-09-08 2025-10-14T09:11:04Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/2445/223661 Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2025.1617674 Frontiers in Immunology, 2025, vol. 16 https://doi.org/10.3389/fimmu.2025.1617674 cc-by (c) Garrido Rodríguez, Vanesa et al., 2025 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Frontiers Media Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))