High frequency apoptosis of recent thymic emigrants in the liver of lymphopenic diabetes-prone BioBreeding rats.
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.
Iwakoshi
N N
NN
Department of Medicine, University of Massachusetts Medical School, Worcester 01655, USA.
Goldschneider
I
I
Tausche
F
F
Mordes
J P
JP
Rossini
A A
AA
Greiner
D L
DL
D000818:Animals; D017209:Apoptosis; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D008099:Liver / Q000276:immunology / Q000503:physiopathology*; D008231:Lymphopenia / Q000150:complications / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D011948:Receptors, Antigen, T-Cell