Abstract:
:Insulin-dependent diabetes (type 1 diabetes) in the NOD mouse is a T-cell-mediated autoimmune disease. However, B-cells may also play a critical role in disease pathogenesis, as genetically B-cell-deficient NOD mice (NOD.microMT) have been shown to be protected from type 1 diabetes and to display reduced responses to certain islet autoantigens. To examine the requirements for B-cells in the development of type 1 diabetes, we generated a B-cell-naive T-cell repertoire by transplantation of NOD fetal thymuses (FTs) into NOD.scid recipients. Surprisingly, these FT-derived NOD T-cells were diabetogenic in 36% of NOD.scid recipients, despite the absence of B-cells. In addition, T-cells isolated from NOD.microMT mice were diabetogenic in 22% of NOD.scid recipients. Together, these results indicate that B-cells are not an absolute requirement for the generation or effector function of an islet-reactive T-cell repertoire in NOD mice. We suggest that conditions favoring rapid lymphocyte expansion can reveal autoreactive T-cell activity and precipitate disease in genetically susceptible individuals.
journal_name
Diabetesjournal_title
Diabetesauthors
Chiu PP,Serreze DV,Danska JSdoi
10.2337/diabetes.50.4.763subject
Has Abstractpub_date
2001-04-01 00:00:00pages
763-70issue
4eissn
0012-1797issn
1939-327Xjournal_volume
50pub_type
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