Gut-resident T cells morph into disease-causing natural killer (NK)-like cells during Celiac disease (CD), according to Meresse and colleagues on page 1343.
For people with CD, dietary gluten is the enemy. Gluten consumption somehow stresses the epithelial lining of the gut and triggers the activation of gluten-specific CD4+ T cells. CD8+ cytolytic T lymphocytes (CTLs) in the gut also expand during CD, but their role in disease is less clear.
Meresse and colleagues now show that gut CTLs from patients with CD express high levels of the activating NK cell receptor NKG2C, which is typically expressed only by NK cells. Binding of NKG2C by its receptor HLA-E (which was expressed on diseased gut epithelium) caused the CTLs to kill NK target cell lines, proliferate, and produce interferon (IFN)-γ—all in the absence of T cell receptor (TCR) ligation. In short, it caused them...