The contribution of insulitis to diabetes development in tumor necrosis factor transgenic mice.
The inflammatory response mediated by cytokines such as TNF can promote recruitment of lymphocytes to a tissue. Moreover, if other conditions are met, this can provide a predisposing role to autoimmune disease. TNFs induce the appearance of adhesion molecules (and presumably, therefore, extravasation of lymphocytes into tissue from the vasculature) and increase the levels of MHC class I on tissue. However, it is not clear which of these effects plays the key role in induction of disease. This should be the subject of further study. The data substantiate the hypothesis that chronic inflammation might play a precipitating role in autoimmunity and could be one of the environmental factors of importance in the development of so many autoimmune diseases.
Flavell
R A
RA
Section of Immunobiology, FMB 412 Yale University School of Medicine, New Haven, CT 06520-8011, USA.
Kratz
A
A
Ruddle
N H
NH
D000818:Animals; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D007515:Islets of Langerhans; D008214:Lymphocytes / Q000502:physiology; D008233:Lymphotoxin-alpha / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010195:Pancreatitis / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha