Alterations of Specific Lymphocytic Subsets with Ageing and with Aged-Related Metabolic and Cardiovascular Diseases

Abstract

Abstract Ageing of the immune system (immunosenescence (ISC)), is a complex subject characterized by a decrease in cell-mediated immunity, particularly with T-cell function. We conducted a clinical study to analyze peripheral blood (PB) for alterations in T-cell subsets among young healthy (YH) controls, elderly healthy (EH) controls, age-matched subjects with metabolic diseases (MDs; E-MDs), and cardiovascular diseases (CVDs; E-CVDs). The frequencies of expressions of CD3T, CD8T, and invariant natural killer T (NKTs; iNKT) cells were reduced in the EH, E-MD, and E-CVD cohorts; in contrast, CD4T and regulatory T (Treg) cell frequencies tended to increase with ageing, whereas they were lower in subjects with aged-related MDs and CVDs. Moreover, subsets including naïve, effector memory T (TEM) cells, effector memory T cells re-expressing CD45RA (TEMRA), as well as the CD28−CD57+phenotype in the CD4T and CD8T subpopulations consistently showed accumulation of senescent T-cell subsets in ageing, and in patients with E-MDs and E-CVDs compared to YH volunteers. Notably, serum cytokines, including Interferon (IFN)-γ, Transforming growth factor (TGF)-β, and Growth differentiation factor (GDF)-15 levels were consistently reflection of the alterations in T-cell subsets for within-group comparisons. Ageing-, E-MD-, and E-CVD-associated changes in PB T-cell subsets were paralleled by alterations in expressions of cytokines involved in lymphopoiesis, which might play important roles in ageing, and aged-related MD- and CVD-mediated dysregulation of immune functions. Furthermore, identifying these altered T-cell subsets can potentially serve as diagnostic markers for preventing ageing problems and treating aged-related MDs and CVDs.