Table 1.
Summary of estimates of CD8+ T cell generation and proliferation rates in humans.
| Population | Phenotype | Generation rate (d−1) | Range (d−1) | Proliferation rate (d−1) | Range (d−1) | Source | Method | Notes |
|---|---|---|---|---|---|---|---|---|
| Naïve | CD45RA+ | 0.002 [100% self-renewal, 0% from thymus [19]] | 0.0–0.01 | 0.002 | 0.0–0.01 | Macallan et al. [13] Table 1a | 1d 2H2-glu kh model | Based on best phenotypic definition at time. Will inadvertently have included TEMRA and TSCM. |
| CD45RO―CD27+ | 0.0003 | 0.0003–0.0005 | 0.0003 | 0.0003–0.0005 | Vrisekoop et al. [16] Table 1a | 63d 2H2O kh model | Based on best phenotypic definition at time. Will inadvertently have included TSCM. | |
| CD45RO―CD27brightCCR7+CD95― |
0.00045 |
0.0003–0.0006 |
0.00045 |
0.0003–0.0006 |
Costa del Amo et al. [18] Table S2a |
49d 2H2O precursor model |
||
| TSCM |
CD45RO―CD27brightCCR7+CD95+ |
0.01 [64% self-renewal, 35% from naïve pool [18]] |
0.006–0.07 |
0.007 |
0.002–0.01 |
Costa del Amo et al. [18] Table 1 and S2 (see notes) |
49d 2H2O precursor model |
Paper found evidence for ≥ two subpopulations. Here we report the average rates derived from Table 1 (ratio of subpopulations) and Table S2 (proliferation and disappearance of subpopulations) |
| Memory | CD45RA― | 0.019 | 0.006–0.16 | Macallan et al. [13] Table 1¥ | 1 d 2H2-glu kh model | Later corrected by Ahmed et al. see below | ||
| CD45RO+ | 0.0028 | 0.0019–0.006 | Vrisekoop et al. [16] Table 1¥ | 63d 2H2O kh model | Later corrected by Westera et al. and Ahmed et al. see below | |||
| CD45RO+ | 0.006 | 0.004–0.009 | Westera et al. [27] in line text (note typo on upper limit of range in original paper, corrected here)¥ | 63d 2H2O multi-exp model | Corrected analysis of Vrisekoop et al. data | |||
| CD45RA― | 0.015 | 0.006–0.11 | Ahmed et al. [28] adjustment taken from Table S1 and applied to Macallan estimates¥ | 1d 2H2-glu kh model | Corrected analysis of Macallan et al. data. | |||
| CD45RO+ | 0.007 | 0.004–0.009 | Ahmed et al. [28] adjustment taken from Figure S7 (ratio of bw) and applied to Westera estimates ¥ | 63d 2H2O multi-exp model | Further corrected analysis of Vrisekoop et al. data. |
Estimates (within each subpopulation) provided in chronological order. Estimates shown in bold font are current best estimates, estimates in regular font have been superseded (see final column, notes). All estimates, with the exception of the TSCM subpopulation parameters, assume there is no input from a precursor population (Box 1). Work from Westera et al. indicates this is a valid assumption for naïve cells. However, for memory cells we cannot necessarily neglect input from the precursor population (in this case naïve cells). Proliferation rate estimates marked ¥ may therefore need to be revised when additional data are available.
All rates provided as proportion of target cell population and represent the median across study individuals.
Abbreviations: D2-glu: D2-glucose, kh model: kinetic heterogeneity model, multi-exp model: multi-exponential model.
Model equations provided in Supplementary Information.
The range is the minimum and maximum value of the point estimate observed across the subjects.
Proliferation rate estimate for naïve cells calculated from production rate based on the finding that 100% of new naïve cells in humans originate from peripheral proliferation [19].