High frequency apoptosis of recent thymic emigrants in the liver of lymphopenic diabetes-prone BioBreeding rats
Authors
Iwakoshi, Neal N.Goldschneider, Irving
Tausche, Frances
Mordes, John P.
Rossini, Aldo A.
Greiner, Dale L.
UMass Chan Affiliations
Department of Medicine, Diabetes DivisionProgram in Molecular Medicine
Program in Immunology and Virology
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
1998-06-24Keywords
Animals; *Apoptosis; Diabetes Mellitus, Type 1; Female; Liver; Lymphopenia; Male; Rats; Rats, Inbred BB; Receptors, Antigen, T-Cell; T-LymphocytesLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Diabetes-prone (DP) BioBreeding (BB) rats develop spontaneous autoimmune diabetes. DP-BB thymocyte export is reduced, and most thymic emigrants disappear rapidly from peripheral lymphoid tissues. DP-BB rats are consequently lymphopenic and circulate severely reduced numbers of T cells. Peripheral T cells present are phenotypically immature (Thy1+) and appear activated. We hypothesized that DP-BB recent thymic emigrants have a shortened life span and disappear by apoptosis. The percentage of T cells with an alphabetaTCR(low) B220+ CD4- CD8- phenotype was increased in DP peripheral lymphoid tissues when compared with normal, nonlymphopenic diabetes-resistant (DR) BB rat tissues. There was no evidence of DNA fragmentation in freshly isolated DP- or DR-BB rat cells, but, after 24 h of culture, a higher proportion of DP- than DR-BB splenic T cells underwent apoptosis. We then tested the hypothesis that BB rat T cells with the alphabetaTCR(low) B220+ CD4- CD8- phenotype accumulate and undergo apoptosis in the liver. Such cells were observed undergoing apoptosis in both DP- and DR-BB rats, but comprised approximately 80% of intrahepatic T cells in DP vs approximately 20% in DR-BB rats. Most alphabetaTCR(low) B220+ CD4- CD8- cells in the liver were also Thy1+. The data suggest that T cell apoptosis in the DP-BB rat is underway in peripheral lymphoid tissues and is completed in the liver. Increased intrahepatic apoptosis of recent thymic emigrants appears in part responsible for lymphopenia in DP-BB rats and the concomitant predisposition of these animals to autoimmunity.Source
J Immunol. 1998 Jun 15;160(12):5838-50.