Gorbachev Anton V, Fairchild Robert L
Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195-0001, USA.
Eur J Immunol. 2006 Sep;36(9):2494-503. doi: 10.1002/eji.200636075.
Activated NKT cells produce cytokines such as IL-4 and IFN-gamma that function locally to influence the strength and functional development of antigen-specific T cells. Here we identify an alternative mechanism by which NKT cells influence the strength of T cell responses: through modulation of peripheral dendritic cell (DC) trafficking. NKT cell activation with alpha-galactosylceramide induced high systemic levels of TNF-alpha that mediated increased DC migration from skin to draining lymph nodes. This increased DC trafficking led to a threefold increase in effector T cell priming and in the immune response elicited to antigen challenge when alpha-galactosylceramide was given at the time of immunization of the skin. These studies provide important implications for the use of NKT cell activation strategies to manipulate T cell-mediated responses including responses to cutaneous tumors and graft vs. host disease.
活化的自然杀伤T细胞（NKT细胞）会产生诸如白细胞介素-4（IL-4）和干扰素-γ（IFN-γ）等细胞因子，这些细胞因子在局部发挥作用，影响抗原特异性T细胞的强度和功能发育。在此，我们确定了一种NKT细胞影响T细胞反应强度的替代机制：通过调节外周树突状细胞（DC）的迁移。用α-半乳糖神经酰胺激活NKT细胞会诱导全身高水平的肿瘤坏死因子-α（TNF-α），该因子介导了DC从皮肤向引流淋巴结的迁移增加。当在皮肤免疫时给予α-半乳糖神经酰胺，这种增加的DC迁移导致效应T细胞启动增加了三倍，并增强了对抗原攻击引发的免疫反应。这些研究对于使用NKT细胞激活策略来操纵T细胞介导的反应具有重要意义，这些反应包括对皮肤肿瘤的反应以及移植物抗宿主病。
