Garrido-Rodríguez, VanesaHerrero-Fernández, InésCastro, María JoséCastillo, AnaRosado-Sánchez, IsaacGalvá, María IsabelRamos, RaquelOlivas-Martínez, IsraelBulnes-Ramos, ÁngelCañizares, JulioLeal, ManuelPacheco, Yolanda María2023-02-092023-02-092021-05-26http://hdl.handle.net/10668/17835The CD4/CD8 T-cell ratio is emerging as a relevant marker of evolution for many pathologies and therapies. We aimed to explore immunological features beyond CD4/CD8 ratio values in older subjects (>65 years old) who were classified as having lower (65 years old) who were classified as having lower (2) ratio values. The lower group showed a lower thymic output (sj/β-TREC ratio) and frequency of naïve T-cells, concomitant with increased mature T-cells. In these subjects, the CD4 T-cell subset was enriched in CD95+ but depleted of CD98+ cells. The regulatory T-cell (Treg) compartment was enriched in CTLA-4+ cells. The CD8 T-cell pool exhibited increased frequencies of CD95+ cells but decreased frequencies of integrin-β7+ cells. Interestingly, in the intermediate group, the CD4 pool showed greater differences than the CD8 pool, mostly for cellular senescence. Regarding inflammation, only hsCRP was elevated in the lower group; however, negative correlations between the CD4/CD8 ratio and β2-microglobulin and sCD163 were detected. These subjects displayed trends of more comorbidities and less independence in daily activities. Altogether, our data reveal different thymic output and immune profiles for T-cells across CD4/CD8 ratio values that can define immune capabilities, affecting health status in older individuals. Thus, the CD4/CD8 ratio may be used as an integrative marker of biological age.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/CD4/CD8 T-cell ratioTRECTreginflammationthymic outputAgedAged, 80 and overCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCTLA-4 AntigenCell CompartmentationComorbidityFemaleHumansInflammationLymphocyte SubsetsMalePhenotypeT-Lymphocytes, RegulatoryThymus Glandresearch article34038386open access10.18632/aging.2031091945-4589PMC8202849https://www.aging-us.com/article/203109/pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202849/pdf