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Thymic epithelial defects and predisposition to autoimmune disease in BB rats.

Publication ,  Journal Article
Doukas, J; Mordes, JP; Swymer, C; Niedzwiecki, D; Mason, R; Rozing, J; Rossini, AA; Greiner, DL
Published in: Am J Pathol
December 1994

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.

Duke Scholars

Published In

Am J Pathol

ISSN

0002-9440

Publication Date

December 1994

Volume

145

Issue

6

Start / End Page

1517 / 1525

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Reference Values
  • Rats, Inbred Strains
  • Rats, Inbred BB
  • Rats
  • Phenotype
  • Pathology
  • Genetic Predisposition to Disease
  • Genes, Dominant
 

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Doukas, J., Mordes, J. P., Swymer, C., Niedzwiecki, D., Mason, R., Rozing, J., … Greiner, D. L. (1994). Thymic epithelial defects and predisposition to autoimmune disease in BB rats. Am J Pathol, 145(6), 1517–1525.
Doukas, J., J. P. Mordes, C. Swymer, D. Niedzwiecki, R. Mason, J. Rozing, A. A. Rossini, and D. L. Greiner. “Thymic epithelial defects and predisposition to autoimmune disease in BB rats.Am J Pathol 145, no. 6 (December 1994): 1517–25.
Doukas J, Mordes JP, Swymer C, Niedzwiecki D, Mason R, Rozing J, et al. Thymic epithelial defects and predisposition to autoimmune disease in BB rats. Am J Pathol. 1994 Dec;145(6):1517–25.
Doukas, J., et al. “Thymic epithelial defects and predisposition to autoimmune disease in BB rats.Am J Pathol, vol. 145, no. 6, Dec. 1994, pp. 1517–25.
Doukas J, Mordes JP, Swymer C, Niedzwiecki D, Mason R, Rozing J, Rossini AA, Greiner DL. Thymic epithelial defects and predisposition to autoimmune disease in BB rats. Am J Pathol. 1994 Dec;145(6):1517–1525.
Journal cover image

Published In

Am J Pathol

ISSN

0002-9440

Publication Date

December 1994

Volume

145

Issue

6

Start / End Page

1517 / 1525

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Reference Values
  • Rats, Inbred Strains
  • Rats, Inbred BB
  • Rats
  • Phenotype
  • Pathology
  • Genetic Predisposition to Disease
  • Genes, Dominant