ATG5-Dependent Autophagy Uncouples T-cell Proliferative and Effector Functions and Separates Graft-versus-Host Disease from Graft-versus-Leukemia.

ABSTRACT: Autophagy is a vital cellular process whose role in T immune cells is poorly understood, specifically, in its regulation of allo-immunity. Stimulation of wild-type T cells in vitro and in vivo with allo-antigens enhances autophagy. To assess the relevance of autophagy to T-cell allo-immunity, we generated T-cell-specific Atg5 knock-out mice. Deficiency of ATG5-dependent autophagy reduced T-cell proliferation and increased apoptosis following in vitro and in vivo allo-stimulation. The absence of ATG5 in allo-stimulated T cells enhanced their ability to release effector cytokines and cytotoxic functions, uncoupling their proliferation and effector functions. Absence of autophagy reduced intracellular degradation of cytotoxic enzymes such as granzyme B, thus

SUBMITTER: Oravecz-Wilson K 

PROVIDER: S-EPMC9400550 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature