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.
1) All patients with PHPT who meet surgical criteria should be referred to an experienced endocrine surgeon to discuss the risks, benefits, and potential complications of surgery. 2) Patients who do not meet surgical criteria and in whom there are no medical contraindications to surgery may request a visit with an experienced endocrine surgeon. Alternatively, a multidisciplinary endocrine conference with surgeon involvement could be employed to address all relevant issues. 3) Imaging is not a diagnostic procedure; it is a localization procedure to help the surgeon optimize the operative plan. 4) The frequency of hereditary forms of PHPT may be underappreciated and needs to be assessed with increased vigilance. And 5) surgery is likely to benefit patients due to high cure rates, low complication rates, and the likelihood of reversing skeletal manifestations.
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