Expression of membrane-bound β-Klotho on peripheral blood CD4+and CD8+T lymphocytes of healthy subjects

Immunosenescence is driven by repeated and continuous immune activation. Sensitive markers are warranted to detect and monitor the process of premature immune ageing. We analysed the ss-Klotho expression on T- cell subsets from healthy donors: young adults, n = 12 (20-30 y); middle-aged, n = 62 (30-50 y) and elderly, n = 18 (> 70 y). The absolute counts (AC) and percentages of total, CD4+, CD8+ and CD8 +CD27-CD57+ T-cells, CD4/CD8 ratio, and the share of ss-Klotho + T-cell subsets were analysed by multicolour flow cytometry. AC of T-cell subsets showed non-significant differences among the groups. The percentages of ss-Klotho(+) total, CD4+ and CD8+ T-cells in young adults exceeded significantly the expression in the elderly and middle-aged subjects: (mean) 2.13 vs. 0.48; 3.23 vs. 0.48; 6.87 vs. 2.28, and 0.75 vs. 2.21; 0.93 vs. 3.32; 6.62 vs. 6.62, respectively (p < 0.05 all). The ss-Klotho expression on total, CD4+ and CD8+ T-cells among middle-aged participants was heterogeneous and significantly higher from the elderly only in CD8 +T-cells (mean): 0.75 vs. 0.47 (p = 0.1); 0.93 vs. 0.72 (p = 1.0) and 3.62 vs 1.75 (p = 0.01), respectively. The proportion of ss-Klotho(+) CD8+ cells did not correlate with age, but correlated inversely and significantly with the share of CD27-CD57 + CD8+ T-cells in middle-aged subjects (R = -0.4, p < 0.01). We hypothesise that CD8 + T-cells showed higher sensitivity to the effects of immune-senescence, at least in part, due to the higher expression and dependence on the effects of KLOTHO gene products. We propose that a reduced share of ss-Klotho + CD8+ T-cells indicates exhaustion due to immune activation, and may serve as an early marker of premature immunosenescence.