TABLE 2.
Agents used to selectively enhance or deplete Tregs in NHP species.
| Agent | Species | Dosage | Reported effect | References |
| Enhancing agents | ||||
| IL-2 | Cynomolgus macaque | 106 IU/m2/day | Increased peripheral blood CD4 and CD8 Tregs (mainly CD45RA– Foxp3hi) | Aoyama et al., 2012 |
| IL-2 | Rhesus macaque | 106 U/m2/day in combination with adoptively-transferred autologous Treg and rapamycin | Doubling of peripheral blood Treg compared with Treg infusion and rapamycin alone; stable expression of Treg gene transcripts | Furlan et al., 2020 |
| IL-2 | Cynomolgus macaque | 0.6–3 × 106 IU/m2 | Acute cellular rejection of tolerated renal allografts 1–10 years post-transplant; reactivation and expansion of alloreactive T effector memory cells | Yamada et al., 2015 |
| AMD3100 (Plerixafor),- antagonist of CXCR4 and CXCL12-mediated chemotaxis | Rhesus macaque | 1 mg/kg (single dose) | CD4+/CD25hiCD127loFoxP3+ Tregs mobilized efficiently using AMD3100-containing regimens; up to fourfold enrichment in leukapheresis products compared with use of G-CSF alone | Kean et al., 2011 |
| GM-CSF and G-CSF | Rhesus macaque | GM-CSF (Leukine; 10 μg/kg/day); G-CSF (Neupogen; 10 μg/kg/day) | Significant elevation of Treg in peripheral blood and leukapheresis products | Sasaki et al., 2020 |
| Depleting agents | ||||
| IL-2-diphtheria toxin fusion protein | Cynomolgus macaque | Two doses (8 or 18 μg/kg) | Rapid, but short-lived decrease in peripheral blood resting Tregs (CD4+CD45RA+Foxp3+) with a transient increase in activated Tregs (CD4+CD45RA–Foxp3hi), followed by their depletion by50–60% | Yamada et al., 2012b |
| Anti-human CCR4 immunotoxin | Cynomolgus macaque | 25 mg/kg twice a day for four consecutive days, 6 h apart | 78–89% CCR4+Foxp3+ Treg reduction in peripheral blood for approx 10 days; 89–96% CCR4+Foxp3+ Treg depletion in lymph nodes | Wang et al., 2016 |
G(M)-CSF, granulocyte (macrophage)-stimulating factor.