Apoptosis of T cells in the hepatic fibrotic tissue of the rat: a possible inducing role of hepatic myofibroblast-like cells

Cell Tissue Res. 2003 Mar;311(3):353-64. doi: 10.1007/s00441-002-0670-4. Epub 2003 Feb 5.

Abstract

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.

MeSH terms

  • Actins / metabolism
  • Animals
  • Apoptosis* / physiology
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / ultrastructure
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / ultrastructure
  • Cell Communication / physiology
  • Cell Differentiation / physiology
  • Chemotaxis, Leukocyte / physiology
  • Concanavalin A / pharmacology
  • Disease Models, Animal
  • Fibroblasts / immunology*
  • Fibroblasts / metabolism
  • Fibroblasts / ultrastructure
  • Hepatitis / immunology*
  • Hepatitis / pathology
  • Hepatitis / physiopathology
  • In Situ Nick-End Labeling
  • Liver Cirrhosis / immunology*
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / physiopathology
  • Male
  • Microscopy, Electron
  • Mitogens / pharmacology
  • Rats
  • Rats, Wistar
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • T-Lymphocytes / ultrastructure

Substances

  • Actins
  • CD3 Complex
  • Mitogens
  • Concanavalin A