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

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 actinpositive 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.

Functional Immune Anatomy of the Liver—As an Allograft

“…Activated state persistence results in fibrosis progression . Nevertheless, when injury resolves, immunomodulation by HSC can instead limit fibrogenesis via (a) anti‐inflammatory mediators such as IL‐10 ; (b) expansion of FoxP3 + regulatory T cells; (c) apoptosis of CD4 + and CD8 + T cells in fibrosis areas ; and (d) stimulation of hepatocyte NO synthesis , which together lead to T cell suppression .…”

Erythrophagocytosis by Liver Macrophages (Kupffer Cells) Promotes Oxidative Stress, Inflammation, and Fibrosis in a Rabbit Model of Steatohepatitis

“…Immunostaining for SM ␣-actin and hemoglobin-␣ was performed using frozen specimens by methods described previously. 27 After being treated with 5% bovine serum albumin/PBS, the specimens were incubated overnight with primary antibodies in 5% bovine serum albumin/PBS. They were then incubated with both 20 g/ml Alexa Fluor 488 goat anti-mouse IgG2a antibodies and 20 g/ml Alexa Fluor 594 goat anti-mouse IgG1 antibodies for 2 hours.…”

“…Electron microscopy was performed on sections of rabbit liver according to methods described elsewhere. 27 The liver was perfusion-fixed with 1.5% glutaraldehyde in 0.0062 mol/L cacodylate buffer, pH 7.4, plus 1% sucrose. The fixed livers were cut into small pieces.…”

Systematic review: hepatic fibrosis – regression with therapy

“…31,32 Furthermore, HSC can also function as antigen presenting cells 33 that can stimulate lymphocyte proliferation or apoptosis. 34 In addition to regulating leucocyte behaviour, HSC may in turn be affected by specific lymphocyte populations, such as CD8 cells which promote more fibrogenic activity towards stellate cells than CD4 cells. 15 The latter may explain in part the increased hepatic fibrosis seen in patients with HCV ⁄ HIV co-infection, where CD4 ⁄ CD8 ratios are reduced, in comparison with patients infected only with HCV.…”