CELL-MEDIATED HYPERSENSITIVITY AND INTERSTITIAL CYSTITIS

间质性膀胱炎（IC）或膀胱疼痛综合征是一种复杂的 病因和发病机制未知的疾病实体。 疾病 主要影响女性，包括各种症状 包括尿频和骨盆疼痛 IC是一种慢性病 膀胱壁的炎性疾病，其特征在于水肿， 纤维化和白细胞浸润以及肥大细胞。 虽然存在 淋巴细胞和巨噬细胞的作用已经在 IC患者的膀胱，关于其性质或贡献 这些细胞及其产物（细胞因子）与IC的发病机制无关。 因此，我们假设IC代表一种疾病，其中膀胱- 特异性细胞介导的超敏反应直接参与 通过T细胞的功能失调调节疾病的发病机制; 巨噬细胞和促炎细胞因子。 调查这一 假设，我们建议首先定义两者的存在 IC血液、尿液和组织中的免疫细胞和细胞因子 患者，并将其存在与临床病史和疾病相关联。 此外，我们还建议描述以下患者的免疫状态： 使用非特异性有丝分裂原从IC患者分离的单核细胞， 以及从尿和膀胱获得的膀胱特异性抗原 组织. 除了评估原发性白细胞的免疫状态外， 从IC患者分离的培养物，我们还计划分离T细胞克隆， 来自IC患者的膀胱组织。 我们也将 表征它们，并评估它们对特异性 膀胱抗原以及膀胱细胞。 最后，我们建议 开发小鼠IC模型。 对于这些研究，我们建议 诱导细胞介导超敏反应和自身免疫 对照和突变小鼠（SCID、Steel和裸鼠），使用最先进的 免疫技术。 因此，使用患者和动物模型，我们 我认为这些研究应该为我们提供重要的新见解， 免疫细胞和免疫产物在膀胱炎中的作用 具体来说

Interstitial cystitis (IC) or painful bladder syndrome is a complex disease entity with unknown etiology and pathogenesis. The disease effects predominantly women and encompasses a variety of symptoms including frequent urination and pelvic pain. IC is a chronic inflammatory disease of the bladder wall, and is characterized by edema, fibrosis and leukocyte infiltrates and mast cells. Although the presence of both lymphocytes as well as macrophages have been demonstrated in the bladders of IC patients, nothing is known about the nature or contribution of these cells nor their products (cytokine) to the pathogenesis of IC. Thus, we have hypothesized that IC represents a disease in which bladder- specific cell-mediated hypersensitivity participates directly in the pathogenesis of the disease by dysfunctional regulation of T cells; macrophages, and proinflammatory cytokines. To investigate this hypothesis, we propose to initially define the presence of both immunologic cells and cytokines within the blood, urine and tissue of IC patients, and correlate their presence with clinical history and disease. Additionally, we propose to characterize the immunologic status of mononuclear cells isolated from IC patients using non-specific mitogens, as well as bladder-specific antigens obtained from urine and bladder tissue. In addition to evaluating the immune status of primary leukocyte cultures isolated from IC patients, we also plan to isolate T cell clones from urinary bladder tissue of patients with IC. Also we will characterize them and evaluate their in vitro responsiveness to specific bladder antigens, as well as bladder cells. Finally, we propose to develop models of IC in the mouse. For these studies, we propose to induce both cell-mediated hypersensitivity and autoimmunity in both control and mutant mice (SCID, Steel and nude mice) using state-of-the-art immunologic techniques. Thus using both patient and animal models, we feel that these studies should provide important new insights into the role of immune cells and products in cystitis in general, and IC specifically.