CD8+ T cells recognizing a neuron-restricted antigen injure axons in a model of multiple sclerosis.

CD8+ T cells outnumber CD4+ cells in multiple sclerosis (MS) lesions associated with disease progression, but the pathogenic role and antigenic targets of these clonally expanded effectors are unknown. Based on evidence that demyelination is necessary but not sufficient for disease progression in MS, we previously hypothesized that CNS-infiltrating CD8+ T cells specific for neuronal antigens directly drive the axonal and neuronal injury that leads to cumulative neurologic disability in patients with MS. We now show that demyelination induced expression of MHC class I on neurons and axons and resulted in presentation of a neuron-specific neoantigen (synapsin promoter-driven chicken ovalbumin) to antigen-specific CD8+ T cells (anti-ovalbumin OT-I TCR-transgenic T cells).

G9a Modulates Lipid Metabolism in CD4 T Cells to Regulate Intestinal Inflammation.

Background & Aims: Although T-cell intrinsic expression of G9a has been associated with murine intestinal inflammation, mechanistic insight into the role of this methyltransferase in human T-cell differentiation is ill defined, and manipulation of G9a function for therapeutic use against inflammatory disorders is unexplored.

Methods: Human naive T cells were isolated from peripheral blood and differentiated in vitro in the presence of a G9a inhibitor (UNC0642) before being characterized via the transcriptome (RNA sequencing), chromatin accessibility (assay for transposase-accessible chromatin by sequencing), protein expression (cytometry by time of flight, flow cytometry), metabolism (mitochondrial stress test, ultrahigh performance liquid chromatography-tandem mas spectroscopy) and function (T-cell suppression assay). The in vivo role of G9a was assessed using 3 murine models.

Fracture characteristics of anterior resin-bonded zirconia-fixed partial dentures.

Resin-bonded fixed partial dentures (RBFPD) are used as a minimal invasive, tooth-preventing alternative for replacing anterior teeth. Zirconia cantilever restorations were supposed to show sufficient strength for a clinical application. The aim of this investigation was to determine the fracture characteristics of cantilever and two-retainer RBFPD, which are fabricated by computer-manufactured high-strength zirconia.