INFLAMMATORY BOWEL DISEASE: NK ACTIVITY IN GUT MUCOSA

炎症性肠病：肠道粘膜中的 NK 活性

• 批准号: 3151797
• 负责人: Stephan R. Targan
• 金额: $ 9.79万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-08-01 至 1988-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3151797
• 关键词: Crohn's disease; epithelium; human tissue; inflammatory bowel diseases; interferons; intestinal mucosa; lymphocyte; ulcerative colitis

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.

该项目的长期目标是获得一个更完整的 了解人体自然杀伤（NK）细胞的生理学 并定义存在于肠组织中的差异， 炎症性肠病（IBD）。 从以前的工作，我们已经建立了一个 IBD免疫异常假说。 我们假设，由于 过度调节淋巴母细胞样B细胞（B细胞，其对于 对外源性抗原的成功抗体应答），体液免疫 低反应性结果。 为了测试这些异常是否 在IBD患者的外周血细胞中已经证明， 在肠道相关淋巴细胞群中起作用，我们测试了 肠道组织中LB细胞的存在。 我们有了初步结果 提示正常肠道中存在IgG和伊加LB细胞， 这些在IBD中的活性降低。 这些结果表明，在 IBD肠道中这种NK细胞的活性可能是导致这种情况的原因 降低LB活性。 这种连续补助金的具体目标是 为了在肠道水平上评估这一假设的有效性， 这些NK细胞亚群在正常和IBD中的存在和活性变化 分离的肠系膜淋巴结和肠淋巴样群体。 具体而言，我们计划（1）定义NK K562亚群的表型 使用单克隆抗体检测IBD肠肠系膜淋巴结中的细胞活性。 （二） 确定正常肠道中存在的NK功能抑制细胞， 组织和IBD标本中的进一步测试活性;（3）研究 对LB细胞有活性的NK细胞的存在、类型和活性水平 在正常和IBD肠和肠系膜淋巴结中，通过a）使用PBL 作为指示靶标的相关LB细胞，B）定义IgG和伊加以及LB c）定义正常肠中PBL NK亚群的活性， 抑制来自正常和IBD肠的LB细胞的功能，和d） 在分离的IgG和伊加LB细胞上测试肠道NK LB细胞的活性 从正常的IBD肠道。 这些研究将使我们能够测试一个模型， 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，它们将大大扩展 我们对NK粘膜细胞的基本生理学知识以及 粘膜抗体应答的终末调节机制 在人类身上。

项目成果

The effect of 6-mercaptopurine on natural killer-cell activities in Crohn's disease.

6-巯基嘌呤对克罗恩病自然杀伤细胞活性的影响。

• DOI: 10.1007/bf00915512
• 发表时间: 1985
• 期刊: Journal of clinical immunology
• 影响因子: 9.1
• 作者: Brogan,M;Hiserodt,J;Oliver,M;Stevens,R;Korelitz,B;Targan,S
• 通讯作者: Targan,S

Isolation of spontaneous and interferon inducible natural killer like cells from human colonic mucosa: lysis of lymphoid and autologous epithelial target cells.

从人结肠粘膜中分离自发的和干扰素诱导的自然杀伤细胞样细胞：裂解淋巴和自体上皮靶细胞。

• 发表时间: 1983
• 期刊: Clinical and experimental immunology
• 影响因子: 4.6
• 作者: Targan,S;Britvan,L;Kendal,R;Vimadalal,S;Soll,A
• 通讯作者: Soll,A

NK and T cell subsets regulate antibody production by human in vivo antigen-induced lymphoblastoid B cells.

NK 和 T 细胞亚群调节人体内抗原诱导的淋巴母细胞 B 细胞的抗体产生。

• 发表时间: 1984
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Brieva,JA;Targan,S;Stevens,RH
• 通讯作者: Stevens,RH