Biological and immunological characterization of a human liver immunoregulatory protein

The liver immunoregulatory protein (LIP) was originally characterized as human liver-derived soluble factor which inhibited the alloantigen and phytohemagglutinin-induced proliferation of human lymphocytes (1). Soluble extracts prepared under the same experimental conditions from kidney, spleen, heart, lymph nodes, and erythrocytes did not exert any inhibitory activity (2). The purpose of this study was to characterize the immunobiological properties of LIP. In the primary one-way mixed lymphocyte culture, LIP depressed the generation of suppressor T cells which inhibited the lymphocyte proliferation induced by phytohemagglutinin or alloantigens. In addition, LIP suppressed in primary mixed lymphocyte culture the induction of cytotoxic T cells and memory cells as determined by cell-mediated lympholysis and secondary mixed lymphocyte culture, respectively. In the presence of LIP, the concanavalin A-mediated induction of suppressor T cells, the pokeweed mitogen-induced IgG synthesis in vitro and the cytolytic activity of K cells reacting in the antibody-dependent cell-mediated cytotoxicity were also inhibited. Cytotoxic effects could be excluded since the viability of human lymphoblastoid cells, hepatocytes, and allogeneically stimulated lymphocytes was not affected by LIP. LIP was shown to be different from other liver-derived substances like acute phase proteins, immunoregulatory alpha-globulins, C-reactive protein, lipoproteins, and F antigen. Furthermore, LIP is not identical to other serum components like the immunoregulatory rosette inhibition factor and the serum inhibitory factor (3). However, the characteristics described herein strongly indicate that LIP is very similar to the liver extract described by Chisari (4) and the liver-derived inhibitory protein (LIP) described by Grol and Schumacher (5).(ABSTRACT TRUNCATED AT 250 WORDS)