Untersuchung von antigenpräsentierenden Funktionen bei kultivierten hepatischen Sternzellen und transdifferenzierenden Myofibroblasten der Ratte

Studies with liver cells in mice have shown that even cells that are not directly attributed to the immune system can play an antigen-presenting function. The aim of this study was to investigate the behavior of these antigen-presenting hepatic stellate cells (HSC) in rat. Also changes of the antigen-presenting function in the fibrotic liver should be identified on a molecular and functional level. The antigen-presenting function of HSC is both in vitro, in the course of the transdifferentiation of HSC to myofibroblast (MFB), as well as in vivo investigated. Cultured activated HSC express mRNA for all the process of antigen presentation related genes, such as (RT1B, RT1D) (alpha- and beta-chain) of the MHC II complex, and the co-stimulatory molecules CD80 and CD86. The expression, however, decreases during the course of transdifferentiation. After stimulation with the proinflammatory cytokine IFN-gamma, the expression of the MHC II genes RT1B and RT1D on transcriptional and translational (RT1B) level is increasing, while lacking a basal protein expression of RT1B in HSC and MFB. The antigen-presenting function of HSC and MFB was also examined with antigen (gpMBP)- and MHC II (RT1B) specific 53/4 T hybridoma cells. Activated HSC are able to release a RT1B-restricted T-cell answer. They are in principle be able to process and to present antigens. The specific functionality of the activated HSC, however, decreases during the course of transdifferentiation. MFB have a lower capacity for T-cell activation. IFN-gamma stimulation causes not only increased MHC II gene expression in HSC and MFB, but also leads to increased antigen presentation along with increased T-cell activation. The change of immune status and participation of HSC was examined in vivo in two models of liver fibrosis. The one in which the bile duct was ligated (BDL) and the other, where carbon tetrachloride (CCl4) triggers a toxic cell injury. In both model systems, the protein expression of RT1B (MHC II) increases significantly. In the CCl4 model this effect could be demonstrated in addition to Western blot analysis also by immunohistochemical staining. Immunohistochemical staining against RT1B and the HSC-specific protein desmin suggests that activated HSC are the cell type which is responsible for the changed MHC II (RT1B)-cell expression. The results show that, as in mice, activated HSC can take an immunological function in healthy and fibrotic liver.