Thymic epithelial defects and predisposition to autoimmune disease in BB rats.
Journal Article (Journal Article)
We report an association between thymic epithelial defects and predisposition to autoimmunity. Diabetes-prone (DP) BB rats develop spontaneous hyperglycemia and are deficient in T cell subsets expressing the RT6 alloantigen. Diabetes resistant (DR) BB rats become diabetic if depleted of RT6+ T cells. The inciting immune system defects are unknown. We made the following observations: 1) Regions of thymic cortex and medulla devoid of thymic epithelium exist in DP-BB, DR-BB, and Lewis rats, all of which are susceptible to autoimmune disorders. Such defects were absent in eight normal rat strains. 2) Thymic epithelial defects are absent at birth, but present in BB rats at 4 weeks of age. 3) The genetic predisposition to thymic epithelial defects is an autosomal dominant trait. 4) The observation of thymic defects in (DP x WF)F1 rats led to the prediction that such animals, which never develop spontaneous autoimmunity, might be susceptible to its induction. Following depletion of RT6+ T cells we observed diabetes in 91%, and thyroiditis in 43%, of treated F1 animals (n = 23). Pancreatic insulitis was uniformly present. Because thymic epithelium participates in the positive and negative selection of developing thymocytes, we propose that thymic epithelial defects may play an important role in the predisposition of BB rats to autoimmunity.
Full Text
Duke Authors
Cited Authors
- Doukas, J; Mordes, JP; Swymer, C; Niedzwiecki, D; Mason, R; Rozing, J; Rossini, AA; Greiner, DL
Published Date
- December 1994
Published In
Volume / Issue
- 145 / 6
Start / End Page
- 1517 - 1525
PubMed ID
- 7992854
Pubmed Central ID
- PMC1887500
International Standard Serial Number (ISSN)
- 0002-9440
Language
- eng
Conference Location
- United States