T helper (Th) 17 cells represent a novel subset of CD4+ T cells that are protective against extracellular microbes, but are responsible for autoimmune disorders in mice. However, their properties in humans are only partially known. We demonstrate the presence of Th17 cells, some of which produce both interleukin (IL)-17 and interferon (IFN)-γ (Th17/Th1), in the gut of patients with Crohn's disease. Both Th17 and Th17/Th1 clones showed selective expression of IL-23R, CCR6, and the transcription factor RORγt, and they exhibited similar functional features, such as the ability to help B cells, low cytotoxicity, and poor susceptibility to regulation by autologous regulatory T cells. Interestingly, these subsets also expressed the Th1-transcription factor T-bet, and stimulation of these cells in the presence of IL-12 down-regulated the expression of RORγt and the production of IL-17, but induced IFN-γ. These effects were partially inhibited in presence of IL-23. Similar receptor expression and functional capabilities were observed in freshly derived IL-17–producing peripheral blood and tonsillar CD4+ T cells. The demonstration of selective markers for human Th17 cells may help us to understand their pathogenic role. Moreover, the identification of a subset of cells sharing features of both Th1 and Th17, which can arise from the modulation of Th17 cells by IL-12, may raise new issues concerning developmental and/or functional relationships between Th17 and Th1.

Depletion of podocytes, common to glomerular diseases in general, plays a role in the pathogenesis of glomerulosclerosis. Whether podocyte injury in adulthood can be repaired has not been established. Here, we demonstrate that in the adult human kidney, CD133ϩCD24ϩ cells consist of a hierarchical population of progenitors that are arranged in a precise sequence within Bowman's capsule and exhibit heterogeneous potential for differentiation and regeneration. Cells localized to the urinary pole that expressed CD133 and CD24, but not podocyte markers (CD133ϩCD24ϩPDXϪ cells), could regenerate both tubular cells and podocytes. In contrast, cells localized between the urinary pole and vascular pole that expressed both progenitor and podocytes markers (CD133ϩCD24ϩPDXϩ) could regenerate only podocytes. Finally, cells localized to the vascular pole did not exhibit progenitor markers, but displayed phenotypic features of differentiated podocytes (CD133ϪCD24ϪPDXϩ cells). Injection of CD133ϩCD24ϩPDXϪ cells, but not CD133ϩCD24ϩPDXϩ or CD133-CD24Ϫ cells, into mice with adriamycin-induced nephropathy reduced proteinuria and improved chronic glomerular damage, suggesting that CD133ϩCD24ϩPDXϪ cells could potentially treat glomerular disorders characterized by podocyte injury, proteinuria, and progressive glomerulosclerosis. Glomerular diseases account for 90% of ESRD at a cost of $20 billion/yr in the United States. 1 The traditional glomerular disease classification encompasses a bewildering array of descriptive pathologic entities and their clinical counterparts. However, converging evidence suggests that podocyte depletion, secondary to toxic, genetic, immune, infectious, oxidant, metabolic, hemodynamic, and other mechanisms, is a common determining factor that can result in a broad spectrum of clinical syndromes. As long as the podocyte loss is limited, restitution or repair is possible. By contrast, 20 to 40% podocyte loss results in a scarring response, until at greater than 60% podocyte loss glomeruli become globally sclerotic and nonfiltering. These stages of podocyte depletion are accompanied by corresponding degrees of proteinuria and, as an increasing proportion of glomeruli become involved, by measurable reduction in the clearance function of the kidney. [1][2][3] To what extent podocytes can be replaced at all during adult life, and if so, how and at what rate, is still unclear. Indeed, mature podocytes have limited capacity to divide in situ and display all phenotypic and functional features of highly spe-

Recent studies implicated the existence in adult human kidney of a population of renal progenitors with the potential to regenerate glomerular as well as tubular epithelial cells and characterized by coexpression of surface markers CD133 and CD24. Here, we demonstrate that CD1331CD241 renal progenitors can be distinguished in distinct subpopulations from normal human kidneys based on the surface expression of vascular cell adhesion molecule 1, also known as CD106. CD1331CD241CD1061 cells were localized at the urinary pole of Bowman's capsule, while a distinct population of scattered CD1331CD241CD1062 cells was localized in the proximal tubule as well as in the distal convoluted tubule.

Human natural killer (NK) cells comprise 2 main subsets, CD56(bright) and CD56(dim) cells, that differ in function, phenotype, and tissue localization. To further dissect the heterogeneity of CD56(dim) cells, we have performed transcriptome analysis and functional ex vivo characterization of human NK-cell subsets according to the expression of markers related to differentiation, migration or competence. Here, we show for the first time that the ability to respond to cytokines or to activating receptors is mutually exclusive in almost all NK cells with the exception of CD56(dim) CD62L(+) cells. Indeed, only these cells combine the ability to produce interferon-gamma after cytokines and proliferate in vivo during viral infection with the capacity to kill and produce cytokines upon engagement of activating receptors. Therefore, CD56(dim) CD62L(+) cells represent a unique subset of polyfunctional NK cells. Ex vivo analysis of their function, phenotype, telomere length, frequencies during ageing as well as transfer experiments of NK-cell subsets into immunodeficient mice suggest that CD56(dim) CD62L(+) cells represent an intermediate stage of NK-cell maturation, which after restimulation can accomplish multiple tasks and further develop into terminally differentiated effectors.