Asymmetrical Expression of PD1 and CD25 in T-cells Post-Initial Activation

• DOI: 10.4049/jimmunol.210.supp.226.18
• Publication Date: 2023-08-10T02:13:42Z
• Authors: Michael K Sheng; Logan Vick; Craig Collins; Daniel J Yoon; William J Murphy
• Keywords: 0303 health sciences; 03 medical and health sciences

Abstract After TCR engagement, T cells induce expression of CD25, which forms the IL2 high affinity receptor complex, concurrently with PD1, plays a down-regulatory role in activation. Cessation stimulation leads to eventual contraction cell responses. Chimeric antigen (CAR) therapy has seen increased use past decade. CAR T-cells are activated and transduced ex vivo expanded low amounts cytokines prior administration. The CD25 PD1 on at different stages process been incompletely characterized. Purified were vitro for 3 days followed by expansion using dose IL2. We demonstrate that both PD-1 strongly upregulated during initial activation, but day 8, under conditions, is downregulated negligible levels. Despite absence signaling, remains moderate-to-high explaining ability maintain proliferation. This discrepancy was higher compared non-transduced (NT) indicating possibility tonic signaling. Furthermore, restimulation NT CAR-T after this phase resulted further whereas remained low. Our studies suggest engagement necessary PD-1, not expression. However, upon restimulation, capable upregulating These results indicate signaling induces asymmetrical dynamic interplay may regulate T-cell function memory response be limiting factor process.