IMMUNOLOGIC FUNCTION OF LIVER SINUSOIDAL CELLS

各种非淋巴细胞辅助细胞已被证明在免疫系统中起作用。 在诱导和调节免疫反应中起关键作用。 而 肝脏含有大量的候选辅助细胞， 已知它们在局部或全身免疫反应中的作用。 在 在拟议的研究中，将分离人肝窦细胞， 有教养 这个群体中的各种细胞类型将被 其特征在于许多组织化学染色，形态学标准， 细胞表面受体测定和用单克隆抗体染色。 的 这些细胞在体外试验中作为辅助细胞的能力， 将检查免疫应答。 Kupffer法白细胞介素1分泌 细胞或其他正弦细胞将被定量。 的潜力 肝脏各成员之间的免疫调节相互作用 将探索非实质细胞群。 一种成熟的技术 用于分离豚鼠肝窦细胞， 检查这些细胞的体内抗原加工。 在该模型中，抗原 将测定肝脏辅助细胞体内摄取的 通过抗原致敏的T淋巴细胞活化测定的免疫原性 体外 通过这种方法，可以识别肝脏内的细胞， 将确定能够呈递抗原的细胞，并且调节 将检测这种通过免疫刺激的抗原呈递能力。 因此，该建议将检查肝脏的免疫潜力 窦状隙细胞，并试图阐明这种功能的机制， 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.