REDD1 as a stress response gene in mature T cells.

摘要

Regulated in development and DNA damage response 1 (REDD1) is a highly conserved stress response protein that is upregulated following many types of cellular stress including hypoxia, DNA damage, energy stress, ER stress, and nutrient deprivation. In T cells it has been shown to be upregulated following DNA damage and dexamethasone treatment and to provide protection from cell death. In the case of dexamethasone treated thymocytes, REDD1's protection is mediated through the induction of autophagy. However, we know little of REDD1's function in mature T cells. In this study we show that REDD1 is upregulated in mature T cells following stimulation with phytohemagglutinin (PHA) or anti-CD3 and anti-CD28 antibodies immobilized on beads. REDD1 knockout T cells exhibit a defect in proliferation and cell survival, although upregulation of the activation markers CD69 and CD25 and cytokine production appear normal. REDD1 knockdown causes a decrease in productive human immunodeficiency virus (HIV) infection in CD4 T cells. Though the mechanism is unclear, the absence of REDD1 may sensitize HIV infected cells to cell death. Collectively these findings point to a previously unappreciated protective role for REDD1 in mature T cell stress responses.