Islet-Derived eATP Fuels Autoreactive CD8⁺ T Cells and Facilitates the Onset of Type 1 Diabetes.

ABSTRACT: Extracellular ATP (eATP) activates T cells by engaging the P2X7R receptor. We identified two loss-of-function P2X7R mutations that are protective against type 1 diabetes (T1D) and thus hypothesized that eATP/P2X7R signaling may represent an early step in T1D onset. Specifically, we observed that in patients with newly diagnosed T1D, P2X7R is upregulated on CD8⁺ effector T cells in comparison with healthy control subjects. eATP is released at high levels by human/murine islets in vitro in high-glucose/inflammatory conditions, thus upregulating P2X7R on CD8⁺ T cells in vitro. P2X7R blockade with oxidized ATP reduces the CD8⁺ T cell-mediated autoimmune response in vitro and delays diabetes onset in NOD mice. Autoreactive CD8⁺ T-cell activation is hi

SUBMITTER: Tezza S 

PROVIDER: S-EPMC6905486 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature