Fig. 8
From: Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition
Reversal of Treg-induced T-cell senescence by blockage of ATM and STAT signaling in vivo. Pretreatment of naive T cells with ATM inhibitor or STAT signaling inhibitors before co-injection with CD4+CD25hiFoxP3+ Treg cells can significantly block the induction of senescence and reverse the suppressive activity in transferred naive CD8+ T cells in NSG mice. Anti-CD3 activated naive CD8+ T cells (5 × 106 per mouse) were pretreated with the ATM inhibitor KU55933, or STAT1/3 inhibitors MTA or S3I-201 for 24 h, before co-transfer with CD4+CD25hiFoxP3+ Treg ( 2 × 106 per mouse) into NSG mice. The transferred human CD8+ T cells in different organs, including blood, lymph nodes (LN), and spleens (SP) were isolated at 12 days post injection for subsequent SA-β-Gal staining (in a and b), CD28 analysis by flow cytometry (in c), and suppressive activity with the 3H-thymidine incorporation assays (in d and e). *p < 0.05 and **p < 0.01, compared with the medium only group using the ANOVA analysis
