Murine models for systemic lupus erythematosus and Sjögren's syndrome.
Of the types of defects that have been observed in autoimmune mice, two are common to most strains and appear to be of critical importance in the development of autoimmune disease. The first of these is a deficiency in the maintenance of self-tolerance by B or T lymphocytes. This is an intrinsic defect due to genetic abnormalities that presumably affect an early developmental signaling mechanism. The disruption of early B- and T-cell development leads to the appearance of lymphocytes that are predisposed to loss of tolerance. In certain strains of autoimmune mice, it also leads to overproduction of Ly1+ (CD5+) B cells or CD4-CD8-B220+ T cells, which apparently do not contribute to autoimmunity. The second type of defect is a strain-specific, antigen-driven autoimmune disease syndrome. This defect is limited by the affinities of the available T-cell receptor and immunoglobulin variable regions and the efficiency of antigen presentation. Current evidence suggests that the major histocompatibility complex molecules play the most important role in determining which autoantigens lead to a pathogenic antigen-driven immune response. For example, the type and magnitude of the autoimmune response may be directed by the production of specific cytokines. The type of antigen and the context of its presentation can bias the production of cytokines that favor the production of the Th2 subset of CD4+ T helper cells. These cells secrete predominantly interleukin-4, interleukin-5, and interleukin-10, and may contribute to a chronic response and autoimmune disease.
Mountz
J D
JD
University of Alabama, Birmingham.
Gause
W C
WC
Jonsson
R
R
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics; D001402:B-Lymphocytes / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D003920:Diabetes Mellitus / Q000235:genetics; D004195:Disease Models, Animal; D007108:Immune Tolerance; D007135:Immunoglobulin Variable Region / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D008232:Lymphoproliferative Disorders / Q000235:genetics; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell