Role of T cells in development of chronic pancreatitis in male Wistar Bonn/Kobori rats: effects of tacrolimus

Citation
T. Yamada et al., Role of T cells in development of chronic pancreatitis in male Wistar Bonn/Kobori rats: effects of tacrolimus, AM J P-GAST, 281(6), 2001, pp. G1397-G1404
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
ISSN journal
0193-1857 → ACNP
Volume
281
Issue
6
Year of publication
2001
Pages
G1397 - G1404
Database
ISI
SICI code
0193-1857(200112)281:6<G1397:ROTCID>2.0.ZU;2-X
Abstract
We assessed T cell association with acinar cell apoptosis and a preventive effect of tacrolimus, a T cell suppressant, on the development of chronic p ancreatitis in male Wistar Bonn/Kobori rats. At 15 wk, cellular infiltrates composed of F4/80-positive cells (monocytes/macrophages), CD4-positive cel ls, and CD8-positive cells were extensive in the interlobular connective ti ssue and parenchyma. In particular, CD8-positive cells invaded pancreatic l obules and formed close associations with acinar cells, some of which demon strated features of apoptosis. At 20 wk, CD8-positive cells were still abun dant in the fibrotic tissue formed with loss of acinar cells. Repeated subc utaneous injection of 0.1 mg.kg(-1).day(-1) but not 0.025 mg.kg(-1).day(-1) of tacrolimus for 10 wk completely prevented the occurrence of acinar cell apoptosis, infiltration of CD4- and CD8-positive cells, and development of pancreatitis at the age of 20 wk, but these maneuvers did not recover the decreased plasma corticosterone levels, which may be responsible for the de velopment of disease. We demonstrated that T cells, possibly CD8-positive c ells, are involved in inducing apoptosis of acinar cells, raising the possi bility that tacrolimus might find clinical application in the treatment of autoimmune chronic pancreatitis.