IMMUNOLOGIC FUNCTION OF LIVER SINUSOIDAL CELLS

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A variety of non-lymphocyte accessory cells have been shown to play a crucial role in the induction and regulation of immune responses. While the liver contains a large number of candidate accessory cells, little is known about their role in local or systemic immune responses. In the proposed studies, human liver sinusoidal cells will be isolated and cultured. The various cell types within this population will be characterized by a number of histochemical stains, morphological criteria, cell surface receptor assays, and staining with monoclonal antibodies. The ability of these cells to serve as accessory cells in in vitro assays of immune responsiveness will be examined. Interleukin 1 secretion by Kupffer cells or other sinusoidal cells will be quantitated. The potential for immunomudalatory interactions between various members of the hepatic non-parenchymal cell population will be explored. An established technique for isolation of guinea pig liver sinusoidal cells will be utilized to examine in vivo antigen processing by these cells. In this model, antigen taken up in vivo by liver accessory cells will be assayed for immunogenicity as determined by activation of antigen primed T lymphocytes in vitro. By this method, the identity of cells within the liver which are capable of presenting antigen will be determined, and the modulation of such antigen presenting ability by immunologic stimuli will be examined. Thus, this proposal will examine the immunologic potential of liver sinusoidal cells and seek to elucidate mechanisms by which such function is modulated within the microenvironment of the liver.