Apoptosis of T cells in the hepatic fibrotic tissue of the rat: a possible inducing role of hepatic myofibroblast-like cells.
Apoptosis of T cells contributes to the immune homeostasis in inflamed organs. A prominent T-cell infiltration is usually seen in human chronic active hepatitis, being associated with liver fibrosis. In order to demonstrate T-cell apoptosis in the hepatic fibrotic tissue, we induced T-cell infiltration in the fibrotic liver of the rat by injecting concanavalin A (Con A), a T-cell mitogen. Lymphocytes increased in number with a peak at 1 day, preferentially distributing in the fibrotic tissue rather than the parenchyma. They consisted of CD4-positive and CD8-positive cells, and gave the feature of lymphoblasts. Double staining for CD3 and TUNEL demonstrated that T cells underwent apoptosis. Apoptotic cells were more frequent in the fibrotic livers than the normal livers, and were spatially associated with alpha-smooth muscle actin-positive myofibroblast-like cells that possibly derived from hepatic stellate cells (HSCs) and portal fibroblasts through activation. In vitro experiments demonstrated that lymphocyte apoptosis was more frequently induced in the co-culture of Con A-activated splenic T cells/activated HSCs compared to that induced in activated T cells/quiescent HSCs or resting T cells/activated HSCs. The present results indicate that T cells which have extravasated and infiltrated the hepatic fibrotic tissue undergo apoptosis probably through an interaction with myofibroblast-like cells, suggesting the regulatory role of the latter cells in T-cell accumulation in the fibrotic liver.
Kobayashi
Sawako
S
Department of Anatomy, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, 545-8585, Osaka, Japan. sawako@med.osaka-cu.ac.jp
Seki
Shuichi
S
Kawada
Norifumi
N
Morikawa
Hiroyasu
H
Nakatani
Kazuki
K
Uyama
Naoki
N
Ikeda
Kazuo
K
Nakajima
Yuji
Y
Arakawa
Tetsuo
T
Kaneda
Kenji
K
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D003208:Concanavalin A / Q000494:pharmacology; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D006505:Hepatitis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D008103:Liver Cirrhosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008854:Microscopy, Electron; D008934:Mitogens / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure
D000199:Actins; D017252:CD3 Complex; D008934:Mitogens; D003208:Concanavalin A