IMMUNOLOGIC FUNCTION OF LIVER SINUSOIDAL CELLS

各种非淋巴细胞辅助细胞已被证明在 在诱导和调节免疫反应中起着至关重要的作用。而当 肝脏含有大量的候选辅助细胞，很少是 已知它们在局部或系统免疫反应中的作用。在 建议的研究，人的肝窦细胞将被分离和 有教养的。这一群体中的各种细胞类型将是 以一些组织化学染色，形态标准， 细胞表面受体分析，并用单抗染色。这个 这些细胞在体外检测中作为辅助细胞的能力 将检查免疫反应性。枯否细胞分泌白细胞介素1 细胞或其他正弦细胞将被定量。潜在的 肝脏不同成员之间的免疫调节相互作用 将探索非实质细胞群体。一种成熟的技术 为分离豚鼠肝脏，将利用肝窦细胞 检查这些细胞在体内对抗原的处理。在这个模型中，抗原 在体内被肝脏辅助细胞摄取的将被检测 抗原诱导的T淋巴细胞活化后的免疫原性 在试管中。通过这种方法，肝脏内细胞的身份是 能够提呈抗原的能力将被确定，并调节 这种通过免疫刺激提呈抗原的能力将被检测。 因此，这项建议将检查肝脏的免疫学潜力。 并试图阐明这种功能是如何被 在肝脏的微环境中进行调节。

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.