Analysis of antigen-presenting functionality of rat hepatic stellate cells

Introduction: The classical functions of hepatic stellate cells (HSCs) are fat storage, vitamin A uptake and metabolism [1]. In response to cellular stress, HSCs transdifferentiate into myofibroblasts (MFB) and produce extracellular matrix proteins. Therefore, they have been implicated in the development if liver fibrosis and subsequent cirrhosis [2]. Recent investigations showed the antigen presentation capability of HSC [3–5]. Human and mice HSCs express genes typical for antigen- presenting cells (APC) including major histocompatibility complex (MHC) class II and the co-stimulatory molecules CD80 and CD86.

Aim: The present study aims to demonstrate that rat HSC have APC functionality.

Methods: Characterization of surface expression of MHC II (RT1B, RT1D) and the major co-stimulatory molecules B7–1 (CD80) and B7–2 (CD86) by FACS analysis and PCR. Antigen presentation was demonstrated in co-culture with antigen specific hybridoma T cells which were induced to produce Interleukin 2 (IL-2) as measured in sandwich ELISA. Detailed cellular properties associated with APC functionality (e. g. phagocytotic processes, antigen processing, and presentation) were investigated.

Results: We showed that rat HSC express all necessary markers necessary to mediate APC functionality including MHC II and co-stimulatory molecules. In co-culture, HSC can present antigen to hybridoma T cells and activate this cells. Activated T cells showed higher proliferation and produced higher quantities of IL-2.

Conclusions: We here present data demonstrating that activate HSC from rat express all necessary molecules necessary for APC functionality. Therefore, we conclude that activated HSC play a role in immune function of the liver. In further studies we will analyse the functionality of MFB.

Literatur: [1] Geerts A. History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. Semin. Liver Dis. (2001) 21: 311-335 [2] Gressner AM et al. Roles of TGF-β in hepatic fibrosis. Front. Biosci. (2002) 7: d793-d807 [3] Winau F et al. Ito cells are professional liver-resident APCs for activating T cell responses. Immunity (2007) 26: 117-129. [4] Vinas O et al. Human hepatic stellate cells show features of antigen-presenting cells and stimulate lymphocyte proliferation. Hepatology (2003) 38: 919-929. [5] Maubach G et al. Expression and upregulation of cathepsin S and other early molecules required for antigen presentation in activated hepatic stellate cells upon IFN-γ treatment, BBA (2007) 1773: 219-231

IL-2 - MHCII - antigen presenting cells - fibrogenesis - hepatic stellate cells