Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development

Int Immunol. 2005 Mar;17(3):307-14. doi: 10.1093/intimm/dxh210. Epub 2005 Jan 31.


A dendritic cell (DC) imbalance with a marked deficiency in CD4- 8+ DC occurs in non-obese diabetic (NOD) mice, a model of human autoimmune diabetes mellitus. Using a NOD congenic mouse strain, we find that this CD4- 8+ DC deficiency is associated with a gene segment on chromosome 4, which also encompasses non-MHC diabetes susceptibility loci. Treatment of NOD mice with fms-like tyrosine kinase 3 ligand (FL) enhances the level of CD4- 8+ DC, temporarily reversing the DC subtype imbalance. At the same time, fms-like tyrosine kinase 3 ligand treatment blocks early stages of the diabetogenic process and with appropriately timed administration can completely prevent diabetes development. This points to a possible clinical use of FL to prevent autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Chromosomes, Human, Pair 4 / genetics
  • Dendritic Cells / immunology*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Disease Models, Animal
  • Humans
  • Membrane Proteins / therapeutic use*
  • Mice
  • Mice, Inbred NOD
  • Mutation


  • Antigens, Differentiation, T-Lymphocyte
  • CD4 Antigens
  • CD8 Antigens
  • Membrane Proteins
  • flt3 ligand protein