The line graph in Panel A shows the percentage of peak deuterium level over time, measured in days after infusion. The x-axis represents days after infusion, ranging from 0 to 400, and the y-axis represents the percentage of peak deuterium level, ranging from 0 to 100 percent. The line graph includes three data series: black lines for patients who received Tregs alone, dark red lines for patients who received Tregs followed by two rounds of daily IL-2 infusion, and light pink lines for patients who received Tregs followed by one round of daily IL-2 infusion. Thin dotted lines represent individual patient data, while thick solid lines represent the nonlinear two-phase decay fit of the group. The bar graph in Panel B shows normalized deuterium enrichment at 6 months and 1 year after infusion for the three groups of patients. The x-axis represents time points (6 months and 1 year), and the y-axis represents the percentage of peak deuterium level, ranging from 0 to 80 percent. The bar graph includes three data series: gray bars for patients who received Tregs alone, light pink bars for patients who received Tregs followed by one round of daily IL-2 infusion, and dark red bars for patients who received Tregs followed by two rounds of daily IL-2 infusion. Statistical significance is indicated with P values. The graphs show that patients who received Tregs followed by two rounds of daily IL-2 infusion have higher deuterium levels over time compared to the other groups.
Pharmacokinetics of infused Tregs in the peripheral blood of type 1 diabetes patients. FACS-purified autologous Tregs were expanded ex vivo in medium containing deuterated glucose, which resulted in the enrichment of deuterium in the genome of the expanded Treg products. Percentage of deuterium enrichment in the peripheral blood Tregs can then be used to assess the pharmacokinetics of the Tregs after infusion. (A) Deuterium signals in peripheral blood over time. The black lines are results from patients who received Tregs alone. The dark red lines are results from patients who received Tregs followed by two rounds of daily IL-2 infusion given between days 3–7 and 42–46. The light pink lines are results from patients who received Tregs followed by one round of daily IL-2 infusion given between days 3–7. The thin dotted lines are data for individual patients, and the thick solid lines are the nonlinear two-phase decay fit of the group (R2 for no IL-2, 1× IL-2, and 2× IL-2 are 0.7721, 0.7209, and 0.4603, respectively). All data are normalized to peak deuterium enrichment detected between day 1 and 14 after cell infusion. (B) Normalized deuterium enrichment at 6 mo and 1 year after infusion in the three groups of patients were compared. Statistical significance was determined using mixed-effects analysis followed by Dunnett’s multiple comparisons test. Only statistically significant P values are listed. Results shown are a reanalysis of previously published data (Bluestone et al., 2015; Dong et al., 2021).