Role of T cells in development of chronic pancreatitis in male Wistar Bonn/Kobori rats: effects of tacrolimus.
We assessed T cell association with acinar cell apoptosis and a preventive effect of tacrolimus, a T cell suppressant, on the development of chronic pancreatitis in male Wistar Bonn/Kobori rats. At 15 wk, cellular infiltrates composed of F4/80-positive cells (monocytes/macrophages), CD4-positive cells, and CD8-positive cells were extensive in the interlobular connective tissue and parenchyma. In particular, CD8-positive cells invaded pancreatic lobules and formed close associations with acinar cells, some of which demonstrated features of apoptosis. At 20 wk, CD8-positive cells were still abundant in the fibrotic tissue formed with loss of acinar cells. Repeated subcutaneous injection of 0.1 mg x kg(-1) x day(-1) but not 0.025 mg x kg(-1) x 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 development of disease. We demonstrated that T cells, possibly CD8-positive cells, are involved in inducing apoptosis of acinar cells, raising the possibility that tacrolimus might find clinical application in the treatment of autoimmune chronic pancreatitis.
Yamada
T
T
First Department of Internal Medicine, Nagoya City University Medical School, Nagoya 467-8601, Japan. yamtmaki@med.nagoya-cu.ac.jp
Hashimoto
T
T
Sogawa
M
M
Kobayashi
S
S
Kaneda
K
K
Nakamura
S
S
Kuno
A
A
Sano
H
H
Ando
T
T
Kobayashi
S
S
Aoki
S
S
Nakazawa
T
T
Ohara
H
H
Nomura
T
T
Joh
T
T
Itoh
M
M
D000818:Animals; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D003345:Corticosterone / Q000097:blood; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D008297:Male; D010195:Pancreatitis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology*; D016559:Tacrolimus / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D003345:Corticosterone; D016559:Tacrolimus