Immunological features beyond CD4/CD8 ratio values in older individuals

• DOI: 10.18632/aging.203109
• Publication Date: 2021-05-26T15:44:00Z
• Authors: Vanesa Garrido-Ro...; Inés Herrero-Fern...; María José Castro; Ana Castillo; Isaac Rosado-Sánchez; María Isabel Galvá; Raquel Ramos; Israel Olivas-Mar...; Ángel Bulnes-Ramos; Julio Cañizares; Manuel Leal; Yolanda María Pac...
• Keywords: CD4-Positive T-Lymphocytes; Male; 0301 basic medicine; Comorbidity; Thymus Gland; CD8-Positive T-Lymphocytes; T-Lymphocytes, Regulatory; 03 medical and health sciences; Humans; CTLA-4 Antigen; TREC; Aged; Aged, 80 and over; Inflammation; CD4/CD8 T-cell ratio; Lymphocyte Subsets; Cell Compartmentation; 3. Good health; Treg; thymic output; Phenotype; inflammation; Thymic output; Female; Research Paper

The 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 (<1.4), intermediate (1.4-2), or higher (>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.