[Role of Fas, FasL in NOD insulitis].

OBJECTIVE

To analyze the significance of Fas-FasL in NOD insulitis and to explore the mechanism of the autoimmune diabetes.

METHODS

Thirty-two female NOD mice, 3-32 weeks of age, were selected. The blood glucose concentrations were recorded. The pathological data were obtained from the HE staining of the pancreatic sections and the immunohistochemical staining, in which insulin, Fas, FasL, CD8 were detected.

RESULTS

Diabetes was found from the age of 14 weeks. In normal islets, insulin + cells accounted for (59.37 +/- 1.21)%, and some islet cells were observed expressing Fas. At the age of 6 weeks, insulitis lesions could be found. The average score of insulitis tended to rise with the increasing age (P < 0.0005). Meanwhile, insulin + cells decreased (P < 0.0005), and correlated negatively with scoring (P < 0.05). Fas+ islet cells increased (P < 0.0005), correlated positively with scoring (P < 0.01). In insulitis lesions, islet cells expressed FasL that increased gradually (P < 0.0005) and correlated positively with scoring (P < 0.01). The infiltrating cells were all Fas negative. But these mononucleated cells showed the expression of FasL and CD8, both increasing gradually (P < 0.0005). Furthermore, there was certain correlation between the expression of some antigens: in islet cells, between Fas and insulin (negative, P < 0.01), insulin and FasL (negative, P < 0.01), and Fas and FasL (positive, P < 0.01). In the infiltrating cells, the expression of CD8 was correlated with FasL (positively, P < 0.01); it was also found that there was a negative correlation between Fas+ islet cells and CD8+ mononucleated cells (P < 0.05).

CONCLUSION

To sum up, there may be some important and complicated effects by Fas-FasL on the damage of beta cells and the regulation of autoreactive T cells in NOD insulitis, which will facilitate further studies in human type 1 diabetes.