The administration of alpha-GalCer-pulsed APCs into the nasal submucosa was found to be safe and induce anti-tumor activity in some patients.

Vα14 NKT cells exhibit various immune regulatory properties in vivo, but their precise mechanisms remain to be solved. In this study, we demonstrate the mechanisms of generation of regulatory dendritic cells (DCs) by stimulation of Vα14 NKT cells in vivo. After repeated injection of α-galactosylceramide (α-GalCer) into mice, splenic DCs acquired properties of regulatory DCs in IL-10-dependent fashion, such as nonmatured phenotypes and increased IL-10 but reduced IL-12 production. The unique cytokine profile in these DCs appears to be regulated by ERK1/2 and IκBNS. These DCs also showed an ability to suppress the development of experimental allergic encephalomyelitis by generating IL-10-producing regulatory CD4 T cells in vivo. These findings contribute to explaining how Vα14 NKT cells regulate the immune responses in vivo.

No abstract

Human invariant Vα24+ natural killer T (NKT) cells display potent antitumor activity upon stimulation. Activation of endogenous Vα24+ NKT cells would be one strategy for the treatment of cancer patients. For example, dendritic cells (DCs) loaded with a glycolipid NKT cell ligand, α‐galactosylceramide (αGalCer, KRN7000), are a possible tool for the activation and expansion of functional Vα24+ NKT cells in vivo. In this report, we demonstrate that the levels of expansion and the ability to produce IFN‐γ of Vα24+ NKT cells induced by αGalCer‐loaded whole PBMCs cultured with IL‐2 and GM‐CSF (IL‐2/GM‐CSF‐cultured PBMCs) were superior to those of cells induced by monocyte‐derived CD11c+ DCs (moDCs) developed with IL‐4 and GM‐CSF. Interestingly, CD11c+ cells in the IL‐2/GM‐CSF‐cultured PBMCs showed a mature phenotype without further stimulation and exerted potent stimulatory activity on Vα24+ NKT cells to enable them to produce IFN‐γ preferentially at an extent equivalent to mature moDCs induced by stimulation with LPS or a cytokine cocktail. Cocultivation with CD11c− cells in the IL‐2/GM‐CSF‐cultured PBMCs induced maturation of moDCs. In particular, CD11c−CD3+ T cells appeared to play important roles in DC maturation. In addition, TNF‐α was preferentially produced by CD11c−CD3+ T cells in IL‐2/GM‐CSF‐cultured PBMCs and was involved in the maturation of moDCs. Thus, the maturation of DCs induced by CD11c− T cells through TNF‐α production appears to result in the efficient expansion and activation of Vα24+ NKT cells to produce IFN‐γ preferentially. © 2005 Wiley‐Liss, Inc.

Thoracic endovascular aortic repair (TEVAR) for thoracic aortic disease constitutes a paradigm shift in the treatment strategy of aortic dissection, as well as thoracic aortic aneurysms. Conventionally, most patients with Stanford type B acute aortic dissection are treated using conservative medical treatment during the acute phase. However, in patients with complicated type B aortic dissection who present with life-threatening complications, TEVAR has been introduced as a novel and less-invasive alternative and has shown better early results than those observed with conventional therapy. Recently, TEVAR was reported to be effective in not only promoting thrombosis of the false lumen but also in preventing aortic enlargement observed at long-term follow-up. TEVAR has been established as first-line therapy for complicated type B aortic dissection. In contrast, a considerable number of patients who received acute phase medical treatment required surgical intervention for chronic dissecting aortic aneurysms. With the increasing popularity of TEVAR for the treatment of complicated type B aortic dissection, prophylactic and pre-emptive TEVAR has been considered in patients with uncomplicated type B aortic dissection. However, supportive evidence for this strategy is limited, and reassessment is mandatory because it is continuously evolving. Although acute type A aortic dissection is a life-threatening condition, the results of open surgery continue to improve in the modern surgical era. Open surgical treatment is well established and recognized as a gold standard even in the endovascular era. Presently, the application of TEVAR for ascending aortic dissection has undergone a change, and TEVAR is considered a viable rescue option for patients with type A aortic dissection who are not eligible for open surgical repair. However, TEVAR for the descending aorta is well-established treatment for retrograde type A dissection. Several conceptual and technical issues remain unresolved, and technological advances would lead to the development of innovative disease-specific devices and solutions in the future for endovascular treatment of acute aortic dissection. (This is a translation of Jpn J Vasc Surg 2018; 27: 337–345.)