Spontaneous development of autoimmune arthritis due to genetic anomaly of T cell signal transduction: Part 1

Semin Immunol. 2006 Aug;18(4):199-206. doi: 10.1016/j.smim.2006.03.007. Epub 2006 May 19.


A point mutation of the gene encoding ZAP-70, a key signal transduction molecule in T cells, results in spontaneous development of T cell-mediated autoimmune arthritis in mice homozygous for the mutation. The genetic anomaly alters differentiation and selection of T cells in the thymus, leading to thymic production of arthritogenic autoimmune T cells. The arthritogenic T cells persist in the periphery and elicit arthritis when activated by microbial agents that stimulate innate immunity. This model is instrumental in understanding how genetic variations in T cell signal transduction, together with environmental influences, contribute to the development of autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • Humans
  • Polymorphism, Single Nucleotide
  • Signal Transduction*
  • T-Lymphocytes / metabolism*
  • ZAP-70 Protein-Tyrosine Kinase / genetics*


  • ZAP-70 Protein-Tyrosine Kinase