MTOR Inhibition Impairs the Activation and Function of Belatacept-Resistant CD4⁺CD57⁺ T Cells In Vivo and In Vitro.

ABSTRACT: Calcineurin inhibitors have improved graft survival in solid-organ transplantation but their use is limited by toxicity, requiring a switch to another immunosuppressor in some cases. Belatacept is one option that has been shown to improve graft and patient survival despite being associated with a higher risk of acute cellular rejection. This risk of acute cellular rejection is correlated with the presence of belatacept-resistant T cells. We performed a transcriptomic analysis of in vitro-activated cells to identify pathways affected by belatacept in belatacept-sensitive cells (CD4⁺CD57^-) but not in belatacept-resistant CD4⁺CD57⁺ T cells. mTOR was significantly downregulated in belatacept-sensitive but not belatacept-resistant T cells. The inhibit

SUBMITTER: Herr F 

PROVIDER: S-EPMC10142381 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature