Title

Thymic epithelial defects and predisposition to autoimmune disease in BB rats

UMMS Affiliation

Department of Pathology; Department of Medicine, Diabetes Division

Publication Date

12-1-1994

Document Type

Article

Subjects

Aging; Animals; Animals, Newborn; Autoimmune Diseases; Autoimmunity; Epithelium; Genes, Dominant; Genetic Predisposition to Disease; Phenotype; Rats; Rats, Inbred BB; Rats, Inbred Strains; Reference Values; T-Lymphocytes; Thymus Gland

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Am J Pathol. 1994 Dec;145(6):1517-25.

Related Resources

Link to article in PubMed

Journal/Book/Conference Title

The American journal of pathology

PubMed ID

7992854