43 research outputs found
Protecting Vulnerable Road Users from Injury
Aymery Constant and Emmanuel Lagarde discuss policies to protect pedestrians, and pedal and motor cyclists, from injury
Heterogeneity of primary outcome measures used in clinical trials of treatments for intermediate, posterior, and panuveitis
Engaging Medical Students in Research: Reaching Out to the Next Generation of Physician-Scientists
Moving anticoagulation initiation and monitoring services into the community: evaluation of the Brighton and hove community pharmacy service
Outcomes in Cochrane Systematic Reviews Addressing Four Common Eye Conditions: An Evaluation of Completeness and Comparability
Modelling non-systemic pesticide residues in fruits with initial deposit variability and weather effects
Protein kinase C signaling during T cell activation induces the endoplasmic reticulum stress response
T cell receptor (TCR) ligation (signal one) in the presence of co-stimulation (signal two) results in downstream signals that increase protein production enabling naïve T cells to fully activate and gain effector function. Enhanced production of proteins by a cell requires an increase in endoplasmic reticulum (ER) chaperone expression, which is accomplished through activation of a cellular mechanism known as the ER stress response. The ER stress response is initiated during the cascade of events that occur for the activation of many cells; however, this process has not been comprehensively studied for T cell function. In this study, we used primary T cells and mice circulating TCR transgenic CD8+ T cells to investigate ER chaperone expression in which TCR signaling was initiated in the presence or absence of co-stimulation. In the presence of both signals, in vitro and in vivo analyses demonstrated induction of the ER stress response, as evidenced by elevated expression of GRP78 and other ER chaperones. Unexpectedly, ER chaperones were also increased in T cells exposed only to signal one, a treatment known to cause T cells to enter the ‘nonresponsive’ states of anergy and tolerance. Treatment of T cells with an inhibitor to protein kinase C (PKC), a serine/threonine protein kinase found downstream of TCR signaling, indicated PKC is involved in the induction of the ER stress response during the T cell activation process, thus revealing a previously unknown role for this signaling protein in T cells. Collectively, these data suggest that induction of the ER stress response through PKC signaling is an important component for the preparation of a T cell response to antigen