Sara van den Berg

150 Chapter 6 average production rates of T CM and T EM/EMRA cells were, respectively 0.00740 and 0.00722 per day for CD4 + T-cells (270.1% and 263.5% per year) and 0.00351 and 0.00279 per day for CD8 + T-cells (128.1% and 101.8% per year), and thereby both for CD4 + and CD8 + T-cells higher than for their T TN counterparts ( Supplementary Figure 7A, Figure 3C ). CD4 + T EM/EMRA cells had a higher production rate than CD8 + T EM/EMRA cells ( Supplementary Figure 7A, Figure 3C ). Confidence intervals of production rate estimations are presented in Supplementary Figure 7B,C . Median (range) of production rates per day All individuals CMV- individuals CMV+ individuals CD4 + T TN cells 0.00065 (0.00011 – 0.00249) 0.00137 (0.00063 – 0.00179) 0.00030 (0.00011 – 0.00249) CD8 + T TN cells 0.00067 (0.00003 – 0.00370) 0.00097 (0.00014 – 0.00137) 0.00049 (0.00003 – 0.00370) CD4 + T CM cells 0.00740 (0.00322 – 0.00967) 0.00755 (0.00578 – 0.00875) 0.007098 (0.00322 – 0.00967) CD8 + T CM cells 0.00351 (0.00168 – 0.02625) 0.00332 (0.00220 – 0.02625) 0.00460 (0.00168 – 0.00813) CD4 + T EM/EMRA cells 0.00722 (0.00353 – 0.01359) 0.00739 (0.00708 – 0.01359) 0.00678 (0.00353 – 0.00746) CD8 + T EM/EMRA cells 0.00279 (0.00198 – 0.00793) 0.00279 (0.00234 – 0.00793) 0.00263 (0.00198 – 0.00536) CMV-specific CD8 + T-cells 0.00228 (0.00148 – 0.00745) N/A 0.00228 (0.00148 – 0.00745) Table 2. Median (range) of production rates of the different T-cell subsets The average production rate of CD4+ T EM/EMRA cells tends to be lower in CMV+ versus CMV- individuals Next, we investigated whether the increased number of memory T-cells and the upregulation of senescence markers seen in CMV infection were associated with altered T-cell dynamics. Therefore, the production rates of T CM and T EM/EMRA CD4 + and CD8 + cells were compared between CMV- and CMV+ individuals. The deuterium enrichment curves of CMV+ and CMV- individuals were largely overlapping for CD4 + T TN and T CM cells and for all CD8 + T-cell subsets ( Figure 3B ), but CD4 + T EM/EMRA cells seemed to reach lower enrichment levels in CMV+ compared to CMV- individuals ( Figure 3B left lower panel ) . Mathematical modelling confirmed a trend towards a lower production rate of CD4 + T EM/EMRA cells in CMV+ versus CMV- individuals ( p = 0.0952, average production rate of 0.005762 (210.3% per year) and 0.008985 per day (327.85% per year), respectively) ( Figure 3C ). In conclusion, the dynamics of T-cell populations are hardly influenced by CMV infection, apart from a slight decrease in the production rate of CD4 + T EM/EMRA cells in CMV+ individuals.