Immune mechanisms for hepatic fibrogenesis. T-lymphocyte-mediated stimulation of fibroblast collagen production in chronic active hepatitis

Abstract

Lymphocytes can produce soluble factors capable of enhancing fibroblast proliferation and collagen synthesis. T-lymphocytes, adherent cells and undifferentiated peripheral blood mononuclear cells from patients with HBsAg-positive chronic active hepatitis and from HBsAg healthy carriers were triggered with purified HBsAg and tested for their ability to enhance collagen production by human dermal fibroblast cultures. Purified HBsAg did not induce any proliferative response in the mononuclear cell cultures. Addition of patient T-lymphocyte supernates to monolayers of fibroblast consistently resulted in a significant enhancement of collagen production. On the contrary, supernates harvested from adherent cell cultures did not demonstrate any stimulatory activity. We therefore assumed that the observed enhancement of collagen production was probably the result of lymphokine(s) produced by T-lymphocytes. This fibrogenic factor (or factors), which is released by T-cells independently of the presence in vitro of HBsAg, is stable at -80 degrees C, not dialyzable and, by Sephadex G-100 gel filtration, is present in a fraction which collects substances of a molecular weight between 50 000 and 100 000. Mononuclear cell supernates from HBsAg healthy carriers did not influence fibroblast collagen accumulation. These data emphasize the possible role that lymphokines may play in the pathogenesis of fibrosis during the natural history of chronic liver disease.