Organ-specific disease provoked by systemic autoimmunity

Cell. 1996 Nov 29;87(5):811-22. doi: 10.1016/s0092-8674(00)81989-3.


Rheumatoid arthritis (RA) is a chronic joint disease characterized by leukocyte invasion and synoviocyte activation followed by cartilage and bone destruction. Its etiology and pathogenesis are poorly understood. We describe a spontaneous mouse model of this syndrome, generated fortuitously by crossing a T cell receptor (TCR) transgenic line with the NOD strain. All offspring develop a joint disease highly reminiscent of RA in man. The trigger for the murine disorder is chance recognition of a NOD-derived major histocompatibility complex (MHC) class II molecule by the transgenic TCR; progression to arthritis involves CD4+ T, B, and probably myeloid cells. Thus, a joint-specific disease need not arise from response to a joint-specific antigen but can be precipitated by a breakdown in general mechanisms of self-tolerance resulting in systemic self-reactivity. We suggest that human RA develops by an analogous mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / physiopathology*
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / physiopathology*
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Compartmentation / immunology
  • Disease Models, Animal
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Phenotype
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Transgenes / immunology


  • Histocompatibility Antigens Class II
  • Receptors, Antigen, T-Cell