Lack of Sprouty 1 and 2 enhances survival of effector CD8+ T cells and yields more protective memory cells.

摘要: Identifying novel pathways that promote robust function and longevity of cytotoxic T cells has promising potential for immunotherapeutic strategies to combat cancer chronic infections. We show sprouty 1 2 (Spry1/2) molecules regulate the survival memory CD8+ cells. Spry1/2 double-knockout (DKO) ovalbumin (OVA)-specific (OT-I cells) mounted more vigorous autoimmune diabetes than WT OT-I when transferred mice expressing OVA in their pancreatic β-islets. To determine consequence deletion on effector cell development function, we used systemic infection with lymphocytic choriomeningitis virus (LCMV) Armstrong. DKO LCMV gp33-specific P14 survive contraction better generate significantly polyfunctional The larger number displayed enhanced infiltration into infected tissue, demonstrating absence can result increased recall capacity. Upon adoptive transfer naive hosts, controlled Listeria monocytogenes formation functional was associated reduced mTORC1 activity glucose uptake. Reduced p-AKT, p-FoxO1/3a, T-bet expression also consistent accrual. Collectively, loss enhances results protective Deleting antigen-specific may have therapeutic enhancing functionality vivo.