IMMUNE REGULATION OF GLOMERULONEPHRITIS

肾小球肾炎（布莱特氏病）是肾功能破坏的最常见原因，导致患者需要人工肾治疗（透析）和肾移植。肾小球或肾脏滤过物受到炎症的攻击并被破坏。这种攻击通常是自身免疫的，即身体的免疫系统对肾组织失去耐受性，对肾小球发起破坏性攻击。在许多患者中，这种攻击是轻微的，并通过目前的治疗来抑制免疫反应。在其他情况下，目前的治疗不足以抑制攻击，肾脏被破坏。本研究使用肾炎实验模型来研究免疫系统如何损伤肾小球。特别是T细胞如何攻击和介导损伤。这是一个新颖的概念，因为迄今为止一直认为抗体和血液中的其他因素（补体）介导损伤。我们的研究小组是第一个发现T细胞介导肾小球肾炎损伤的小组之一，以前认为T细胞仅由抗体和补体介导。本项目将进一步明确T细胞产生的哪些分子影响肾小球损伤。与非特异性免疫抑制药物(如皮质类固醇、细胞毒性（抗癌）药物或环孢素（一种抗排斥药物）相比，其潜在目标是以一种更特异性的方式关闭T细胞攻击机制。这个项目的一个主要部分将是研究细胞因子的作用，细胞因子是由白细胞产生的激素类分子，介导损伤或调节其他白细胞，在影响损伤和关闭免疫损伤方面的作用。

Glomerulonephritis (Bright's Disease) is the commonest cause of destruction of kidney function that leads to patients requiring artificial kidney treatment (dialysis) and renal transplantation. The glomeruli or filters of the kidney are attacked by inflammation and destroyed. The attack is usually auto-immune, that is the bodys' immune system loses tolerance to kidney tissue and mounts a destructive attack on the glomeruli. In many patients, this attack is mild and resolves with current treatments to dampen the immune response. In others, current treatment is inadequate to dampen the attack and the kidney is destroyed. This research uses experimental models of nephritis to examine how the immune system injures the glomeruli. In particular, how T cells attack and mediate injury. This is a novel concept, as hither to it has been thought antibodies and other factors in the blood (complement) mediate injury. Our group was one of the first to identify T cells mediate injury in forms of glomerulonephritis, previously thought to be solely mediated by antibody and complement. This project will further define which molecules produced by the T cell effect injury of glomeruli. With the potential aim of turning off the T cell attack mechanisms in a more specific way than is achieved by non specific immunosuppressive drugs such as corticosteroids, cytotoxic (anti-cancer) drugs or cyclosporine (an anti-rejection drug). A major part of this project will be to examine the role of cytokines, hormone like molecules that are produced by white cells and mediate injury or regulate other white cells, in effecting injury and in turning off the immune injury.