Elevated apoptosis of peripheral T lymphocytes in diabetic BB rats

Abstract
Thymocytes and peripheral lymphocytes of BioBreeding (BB) diabetes‐prone (BBDP) and diabetes‐resistant (BBDR) rat were analysed by fluorescence‐activated cell sorter (FACS). The number of CD4 CD8, CD4+ CD8, CD4 CD8+ and CD4+ CD8+ subsets was not different between BBDP and BBDR rat thymocytes, whereas spleen and lymph nodes in BBDP rats undergo severe T‐cell lymphopenia. Notably, mature CD4 CD8+[T‐cell receptor (TCR)‐αβ+ and CD5+] cells are certainly present in the BBDP rat thymus, unlike some previous reports, suggesting that the differentiation of CD4 CD8+ from CD4+ CD8+ cells occurs normally in the BBDP rat thymus. As a cause of peripheral T‐cell lymphopenia we suspected apoptosis of recent thymic emigrants. By FACS analysis with fluorescein isothiocyanate‐labelled annexin V, elevated apoptosis was evident in BBDP rat peripheral lymphocytes. Furthermore, terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labelling (TUNEL) staining in BBDP rat splenic sections revealed that a number of TUNEL‐positive cells were observed in the T‐lymphocyte‐rich area. From these results, we postulate that an abnormally elevated apoptosis of peripheral T lymphocytes, but not impaired thymocyte differentiation, is a cause of the peripheral T‐cell lymphopenia in BBDP rats.