Howell C D, Yoder T Y, Vierling J M
University of Colorado School of Medicine, Denver.
Cell Immunol. 1992 Mar;140(1):54-66. doi: 10.1016/0008-8749(92)90176-p.
Mononuclear inflammatory cells (MC) isolated from the livers and spleens of mice with chronic graft-vs-host disease (CGVHD) to minor histocompatibility antigens (B10.D2----BALB/c) show defective proliferation when stimulated with Con A and LPS. In turn, both CGVHD liver and spleen cells suppress the proliferation of mitogen-stimulated normal spleen cells in a genetically unrestricted manner. The suppressor activity of CGVHD spleen cells is mediated by plastic nonadherent null (natural suppressor) cells and involves a soluble suppressor factor(s). In contrast, the suppressor activity of CGVHD liver cells is mediated by macrophages (M phi). In the current studies we show that the suppressor activity of CGVHD liver cells is also mediated by soluble factors and compare the roles of prostaglandins and interferon (IFN)-gamma in mediating defective proliferation and suppressor activities of CGVHD liver and spleen MC. Monoclonal antibody to IFN-gamma partially reversed the defective mitogen-stimulated proliferation of CGVHD spleen MC but had no effect on proliferative response of CGVHD liver MC. Indomethacin did not alter the low proliferative response of either CGVHD liver or spleen MC. Anti-IFN-gamma inhibited the ability of CGVHD spleen cells to suppress proliferation of Con A and LPS-stimulated B10.D2 spleen cells. In contrast, anti-IFN-gamma resulted in a small decrease in the ability of liver MC to suppress Con A (but not LPS)-stimulated cell proliferation. Indomethacin decreased the ability of both CGVHD liver and spleen cells to suppress Con A-stimulated proliferation but had inconsistent effects on LPS-stimulated proliferation. These results show that IFN-gamma and prostaglandins partially mediate the suppressor activity of CGVHD spleen MC. The suppressor activity of CGVHD liver MC also involves prostaglandins but is relatively independent of IFN-gamma.
从小鼠慢性移植物抗宿主病（CGVHD）（针对次要组织相容性抗原，B10.D2→BALB/c）的肝脏和脾脏中分离出的单核炎性细胞（MC），在用刀豆蛋白A（Con A）和脂多糖（LPS）刺激时显示出增殖缺陷。反过来，CGVHD肝脏和脾脏细胞以基因非限制性方式抑制有丝分裂原刺激的正常脾脏细胞的增殖。CGVHD脾脏细胞的抑制活性由塑料非黏附性无活性（天然抑制）细胞介导，并涉及一种可溶性抑制因子。相比之下，CGVHD肝细胞的抑制活性由巨噬细胞（M phi）介导。在当前研究中，我们表明CGVHD肝细胞的抑制活性也由可溶性因子介导，并比较了前列腺素和干扰素（IFN）-γ在介导CGVHD肝脏和脾脏MC的增殖缺陷及抑制活性中的作用。抗IFN-γ单克隆抗体部分逆转了CGVHD脾脏MC有丝分裂原刺激的增殖缺陷，但对CGVHD肝脏MC的增殖反应没有影响。消炎痛没有改变CGVHD肝脏或脾脏MC的低增殖反应。抗IFN-γ抑制了CGVHD脾脏细胞抑制Con A和LPS刺激的B10.D2脾脏细胞增殖的能力。相比之下，抗IFN-γ导致肝脏MC抑制Con A（而非LPS）刺激的细胞增殖的能力略有下降。消炎痛降低了CGVHD肝脏和脾脏细胞抑制Con A刺激的增殖的能力，但对LPS刺激的增殖有不一致的影响。这些结果表明，IFN-γ和前列腺素部分介导了CGVHD脾脏MC的抑制活性。CGVHD肝脏MC的抑制活性也涉及前列腺素，但相对独立于IFN-γ。
