The T cell cometh: interplay between adaptive immunity and cytokine networks in rheumatoid arthritis.
The etiology of autoimmunity in humans remains poorly defined, and animal models provide a unique opportunity to study potential autoimmune mechanisms. A novel model of autoimmune inflammatory arthritis results from a point mutation in the zeta-associated-protein of 70 kDa (ZAP-70), which causes abnormal thymic T cell selection and survival of autoreactive clones. Although the resulting clinical and pathologic abnormalities are clearly T cell-dependent, macrophage and fibroblast cytokines such as IL-1 and TNF-alpha are required for full expression of the disease. The studies of Hata et al. raise the intriguing possibility that traditional proinflammatory cytokine networks represent common effector mechanisms in inflammatory joint diseases such as rheumatoid arthritis. Hence, effective therapeutic interventions can target either unique etiologic pathways related to adaptive immune responses or shared terminal mechanisms.
Firestein
Gary S
GS
Division of Rheumatology, Allergy, and Immunology and Clinical Investigation Institute, University of California San Diego School of Medicine, 9500 Gilman Drive, San Diego, CA 92093-0656, USA. gfirestein@ucsd.edu
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity; D016207:Cytokines / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D018448:Models, Immunological; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases