Minimal change disease constitutes a major cause of nephrotic syndrome. It is regarded as a non-immune-complex mediated primary glomerulopathy and pathogenetically is characterised by podocyte injury and effacement of foot processes; therefore, it is also classified as a type of podocytopathy. T cell dysfunction with increased levels of a soluble glomerular permeability factor has been proposed to play a major role in the pathogenesis of minimal change disease. It has been therefore suggested that a dysfunction of regulatory T cells, the orchestrators of immune homeostasis, could be implicated in perpetuating T cell activation in this condition. However, the actual contribution of regulatory T cell dysfunction in the immunopathogenesis of primary minimal change disease is still largely unclear. We here propose a theoretical model based on the available evidence. 1. Introduction The glomerulus is the functional unit of the kidney responsible for blood filtration, which is the first step in blood purification and the production of urine. Normal functioning of the glomerulus requires the integrity of all three major components of the glomerular filtration barrier, that is, endothelial cells, glomerular basement membrane (GBM), and the visceral epithelial cells or podocytes. Podocytes have cellular projections, or foot processes, which interdigitate with each other and wrap around the capillary loops, leaving spaces in between referred to as slit diaphragms. The slit diaphragms serve as a permeable selective barrier with sieving function allowing filtration of fluid and small solutes while preventing large-molecular-weight plasma components and anionic serum proteins like albumin from passing into the urine. Many glomerular disease processes cause damage and subsequent disruption to the glomerular filtration barrier, eventually leading to pathological glomerular permeability to proteins. If proteinuria exceeds 3.5？g/1.73？m2/day and is accompanied by hypoalbuminaemia, oedema, and/or hyperlipidaemia, the resultant clinical picture is referred to as nephrotic syndrome. Primary minimal change disease (MCD) is a distinct histopathological entity that typically presents with idiopathic nephrotic syndrome. But some patients may develop MCD secondary to use of nonsteroidal anti-inflammatory drugs or a lymphoproliferative disorder. Light microscopy in MCD typically reveals very minor changes such as podocyte enlargement or ectatic capillary loops (Figure 1). At times, diffuse mesangial hypercellularity can also occur. On immunofluorescence, no immunoglobulin
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