Tipping Peter G, Holdsworth Stephen R
Monash University, Department of Medicine, Monash Medical Centre, 246 Clayton Rd, Clayton, Victoria, Australia.
J Am Soc Nephrol. 2006 May;17(5):1253-63. doi: 10.1681/ASN.2005091013. Epub 2006 Apr 19.
Crescent formation in glomerulonephritis (GN) is a manifestation of severe glomerular injury that usually results in a poor clinical outcome. In humans, crescentic GN is frequently associated with evidence of either systemic or organ-specific autoimmunity. T cells play a major role in initiation of adaptive immune responses that lead to crescentic injury. In experimental models of crescentic GN, Th1 predominant immune responses have been shown to promote crescent formation. Perturbation of regulatory T cell function may contribute to development of autoimmune crescentic GN. The presence of T cells and macrophages in crescentic glomeruli, frequently in the absence of humoral mediators of immunity, suggest a dominant effector role for T cells in crescentic GN. The association of cellular immune mediators with local fibrin deposition implicates cell-mediated "delayed-type hypersensitivity-like" mechanisms in crescent formation. Intrinsic renal cells also contribute to T cell-driven effector mechanisms in crescentic GN, via expression of MHC II and co-stimulatory molecules and by production of chemokines and cytokines that amplify leukocyte recruitment and injury.
肾小球肾炎(GN)中的新月体形成是严重肾小球损伤的一种表现,通常导致不良的临床结局。在人类中,新月体性GN常与全身或器官特异性自身免疫的证据相关。T细胞在导致新月体损伤的适应性免疫反应启动中起主要作用。在新月体性GN的实验模型中,已表明以Th1为主的免疫反应会促进新月体形成。调节性T细胞功能的紊乱可能有助于自身免疫性新月体性GN的发展。新月体性肾小球中存在T细胞和巨噬细胞,且常常缺乏免疫体液介质,这表明T细胞在新月体性GN中起主要效应作用。细胞免疫介质与局部纤维蛋白沉积的关联暗示了细胞介导的“迟发型超敏反应样”机制参与新月体形成。固有肾细胞也通过表达MHC II和共刺激分子以及产生趋化因子和细胞因子来放大白细胞募集和损伤,从而在新月体性GN中促成T细胞驱动的效应机制。