Age related human T cell subset evolution and senescence

Abstract

T cells are fundamental effector cells against viruses and cancers that can be divided into different subsets based on their long-term immune protection and immediate immune response effects. The percentage and absolute number of these subsets change with ageing, which leads to a reduced immune response in older individuals. Stem cell memory T cells (T_SCM) represent a small population of memory T cells with enhanced proliferation and differentiation properties that are endowed with high potential for maintaining T cell homeostasis. However, whether these cells change with ageing and gender remains unknown. Here, we assayed the distribution of T_SCM and other T cell subsets in peripheral blood from 92 healthy subjects (44 females and 48 males) ranging from 3 to 88 years old by flow cytometry. We found that CD4+ and CD8+ T_SCM in the circulation have relatively stable frequencies, and the absolute number of CD8+ T_SCM decreased with age; however, the ratio of T_SCM to the CD4+ or CD8+ naïve population increased with age. Unlike the obvious changes in other T cell subsets with age and gender, the stable level of T_SCM in peripheral blood may support their capacity for sustaining long-term immunological memory, while their importance may increase together with ageing.

Keywords: Ageing; Central memory T cells; Effector memory T cells; Immunosenescence; Stem cell memory T cell.

Fig. 1

Peripheral T cell reservoirs decrease with age accompanied by an increase in the ratio of CD4 to CD8 cells. a The gating strategy for the T cell populations is shown. CD3 T cells were gated from the CD45 high population, CD4 and CD8 T subsets were gated from the CD3+ population. The total CD3 and CD8 but not CD4 T cell numbers decreased with age, but the difference between adjacent age groups is not significant; b Correlation and regression analysis of different T cell subsets and ages were calculated. The left represents the frequency, and the right represents the absolute number. The red points and bars represent the R-value and 95% confidence interval of the regression equation, and the P value to the right of the figure indicates the statistical significance of each subset. c The ratio of CD4 to CD8 increases with age, and three types of CD4/CD8 ratios (> 2; 1–2; < 1) have different frequencies in the young (3–59 years) and old (60–88 years) cohorts compared with an age-matched population of normal CD4/CD8 T cells. The group with the inverted CD4/CD8 ratio has a higher percentage of CD28- cells in the CD8 subsets

Fig. 2

Age-related shift in T cell distribution and T_SCM homeostasis. a The gating strategy of the T cell subsets populations T_CM (CCR7 + CD45RO+), T_EM (CCR7-CD45RO+), and T_EF (CCR7-CD45RO-), which were gated from CD4 and CD8 T subsets; naïve T cells (CD28 + CD95-) and T_SCM cells (CD28 + CD95+) were gated from the CCR7 + CD45RO- T cell subset according to the expression of CD28 and CD95. The curves and red arrow represent the gate to be copied to gate the expression of CD95 and CCR7 on CD4+ or CD8+ T cells. b Correlation and regression analysis of different T cell subsets and ages were calculated. The left represents the frequency, and the right represents the absolute number. The red points and bars represent the R-value and 95% confidence R-value of the regression equation. The P value to the right of the figure indicates the statistical significance of each subset, and the red box represents the frequency and absolute number of naïve, T_SCM, T_CM, T_EM, and T_EF, and the blue box represents the relationship between the expression of CD28- and CD95+ and age in the above subsets; c While the absolute numbers of CD4 and CD8 naïve and CD8 T_SCM but not CD4 T_SCM decrease with age, the ratio of CD4 T_SCM to CD8 naïve and CD8 T_SCM to naïve cells linearly increased with age

Fig. 3

The number and percentage of T cell subsets change with ageing. a; c Subjects were divided into 3 groups according to three distinct T cell phases: memory generation (ages: 0–20 years, n = 19), memory homeostasis (ages: 20–60 years, n = 41), and immunosenescence (ages:over 60 years, n = 32). a The overall lengths of the bars indicate the absolute median count of the CD4 populations in the three phases according to our data. The different parts of each bar represent different T cell subsets, and the median percentage of each population is written in their respective position. b Schematic diagram of the ageing contribution to the decrease in T cells and thymic stromal cells and increase in adipocyte in the thymus. This process was accompanied by the accumulation of CD28- and CD95+ T cells in the peripheral blood. c The overall lengths of the bars indicate the absolute median count of CD8 populations in three phases according to our data. The different parts of each bar represent different T cell subsets, and the median percentage of each population is shown in their respective positions