IMMUNOLOGY2026™ Conference Recordings For Attendees-A Critical Role for NKG2D Signaling in beta cell-specific CTL Generation and NOD Diabetes

A Critical Role for NKG2D Signaling in beta cell-specific CTL Generation and NOD Diabetes

Video Transcription

Video Summary

Mary Markiewicz studied how the activating immune receptor NKG2D affects type 1 diabetes in NOD mice. Her lab found that deleting NKG2D had different effects depending on the mouse facility, microbiome status, and sex: little effect in one SPF facility, delayed diabetes in another, and a strong protective effect in germ-free males. Knockout mice also had reduced insulitis, especially with fewer CD8 T cells. Adoptive transfer experiments showed NKG2D on CD8 T cells was critical for diabetes in males but not females.  <br /><br />The team proposes that NKG2D acts early, helping naïve CD8 T cells become cytotoxic T cells in pancreatic lymph nodes. In culture, NKG2D-deficient male CD8 cells made less effector cytokine, while females were less dependent on NKG2D. Markiewicz suggested microbiome- and sex-driven “third signals,” possibly type 1 interferon, may compensate for NKG2D loss. She concluded that combination therapies may be needed for human type 1 diabetes.

Meta Tag

Date April 16, 2026 8:15 AM - 8:30 AM

Room 104AB

Session Cellular & Molecular Mechanisms of Autoreactivity

Speaker Mary Markiewicz

Track Basic Autoimmunity (BA)

Year 2026

Keywords

NKG2D

type 1 diabetes

NOD mice

CD8 T cells

microbiome

April 16, 2026 8:15 AM - 8:30 AM

104AB

Cellular & Molecular Mechanisms of Autoreactivity

Mary Markiewicz

Basic Autoimmunity (BA)

2026