INFLAMMATORY BOWEL DISEASE: NK ACTIVITY IN GUT MUCOSA

这个项目的长期目标是派生出一个更完整的 对人类自然杀伤(NK)细胞生理的认识 并定义存在于肠道组织中的差异 炎症性肠病。从以前的工作中，我们已经建立了一个 IBD免疫异常假说。我们假设，由于 淋巴母细胞B细胞过度调节(B细胞是 NK细胞对外源抗原的成功抗体反应)，体液 低响应性结果。以测试这些异常现象是否 已经在(IBD)患者的外周血细胞中被证明可能 在肠道相关淋巴种群中可操作，我们测试了 肠道组织中可见Lb细胞。我们已经有了初步结果 提示正常肠组织中存在免疫球蛋白G和免疫球蛋白A LB细胞。 炎症性肠病患者上述各因子活性降低。这些结果表明， IBD肠道中这种NK细胞的活性可能与此有关 降低了LB活性。这项延续拨款的具体目的是设计的 要在肠道水平上评估这一假设的有效性，需要测试 正常和IBD患者NK细胞亚群的存在及活性变化 孤立的肠系膜结节和肠淋巴组织群。 具体地说，我们计划(1)确定NK K562亚群的表型 用单抗检测IBD肠系膜结节中的细胞活性。(2) 确定正常肠道中存在的NK功能抑制细胞 组织和进一步检测IBD标本的活性；(3)研究 NK细胞活性的存在、类型和活性水平 在正常和IBD肠和肠系膜结节中使用PBL 相关的Lb细胞作为指示目标，b)定义Ig G和Ig A以及Lb 在正常肠道中的活性，c)定义PBL NK亚群的活性 抑制正常和IBD肠道中的LB细胞功能及d) 肠道NK细胞对分离的免疫球蛋白和免疫球蛋白A的免疫活性检测 取自正常的IBD肠道。这些研究将使我们能够在 肠道水平可能有助于解释相关的潜在免疫 IBD存在调节异常。此外，它们还将大大扩展 我们对NK粘膜细胞的基本生理学和 粘膜抗体应答的末端调控机制 在人类身上。

The long term goals of this project are to derive a more complete understanding of the physiology of natural killer (NK) cells in human intestines and to define differences that exist in intestinal tissue of Inflammatory Bowel Disease (IBD). From previous work we have established a hypothesis for immune abnormalities in IBD. We hypothesize that due to the over regulation of lymphoblastoid B cells (B cells which are essential for successful antibody responses to exogenous antigens) by NK cells, humoral hypo responsiveness results. To test whether these abnormalities which have been demonstrated in peripheral blood cells from (IBD) patients might be operant in gut associated lymphoid populations, we tested for the presence of LB cells in gut tissues. We have preliminary results suggesting existance of IgG and IgA LB cells in normal intestines and decreased activity of these in IBD. These results suggest that over activity of such NK cells in IBD intestines may be responsible for this lowered LB activity. Specific aims of this continuation grant are designed to evaluate the validity of this hypothesis at the gut level by testing for the presence and changes in activity of these NK subsets in normal and IBD isolated mesenteric nodes and intestinal lymphoid populations. Specifically we plan to (1) define the phenotype of subsets of NK K562 cells active in IBD gut mesenteric nodes using monoclonal antibodies. (2) to define the suppressor cell of NK function present in normal intestinal tissue and further test activity in IBD specimens; (3) to study the existence, type, and level of activity of NK cells active against LB cells in normal and IBD intestines and mesenteric nodes by a) using PBL associated LB cells as indicator targets, b) defining IgG and IgA and LB activity in normal intestines, c) defining activity of PBL NK subsets in suppressing the functions of LB cells from normal and IBD intestines and d) testing for activity of gut NK LB cells on separated IgG and IgA LB cells from normal IBD intestines. These studies will allow us to test a model at the intestinal level which may help explain a pertinent underlying immune regulatory abnormality existing in IBD. Moreover, they will greatly extend our knowledge of the basic physiology of NK mucosal cells and the mechanisms involved in the terminal regulation in mucosal antibody response in humans.