Developing a novel model system to target insulin-reactive CD8 T cells

Ann N Y Acad Sci. 2008 Dec:1150:54-8. doi: 10.1196/annals.1447.040.

Abstract

CD8 T cells play an important role in autoimmune diabetes development, and therefore removing these cells may protect against disease. To test this, we designed a novel method using engineered cells (InsCD3-zeta) to target insulin-specific CD8 T cells. Insulin-reactive target cells were cultured with InsCD3-zeta CD8 T cells and cytotoxicity was assessed. Activated, but not naïve, InsCD3-zeta CD8 T cells readily killed insulin-reactive target CD8 T cells. This approach to immunotarget relevant pathogenic CD8 T cells may be a therapeutic option to delay or prevent type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / genetics
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Death / drug effects
  • Cytotoxicity, Immunologic / genetics
  • Cytotoxins / pharmacology
  • Cytotoxins / therapeutic use*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Disease Models, Animal*
  • Female
  • Insulin / metabolism*
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred NOD
  • Mice, Transgenic

Substances

  • CD3 Complex
  • CD3 antigen, zeta chain
  • Cytotoxins
  • Insulin