Yamaura Ayako, Hotta Chie, Nakazawa Masatoshi, Van Kaer Luc, Minami Mutsuhiko
Department of Immunology, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Japan.
Blood. 2008 Apr 15;111(8):4254-63. doi: 10.1182/blood-2007-04-085142. Epub 2008 Feb 12.
Glycolipid-reactive Valpha24(+) invariant natural killer T (iNKT) cells have been implicated in regulating a variety of immune responses and in the induction of immunologic tolerance. Activation of iNKT cells requires interaction with professional antigen-presenting cells, such as dendritic cells (DCs). We have investigated the capacity of distinct DC subsets to modulate iNKT cell functions. We demonstrate that tolerogenic DCs (tolDCs), generated by treatment of monocyte-derived DC with interleukin (IL)-10, induced regulatory functions in human iNKT cells. tolDCs, compared with immunogenic DCs, had reduced capacity to induce iNKT-cell proliferation, but these cells produced large amounts of IL-10 and acquired an anergic phenotype. These anergic Valpha24(+) iNKT cells were able to potently inhibit allogeneic CD4(+) T-cell proliferation in vitro. Furthermore, the anergic Valpha24(+) iNKT cells could suppress DC maturation in vitro. We conclude that the interaction of iNKT cells with tolDCs plays an important role in the immune regulatory network, which might be exploited for therapeutic purposes.
糖脂反应性Vα24(+)不变自然杀伤T细胞（iNKT细胞）参与调节多种免疫反应并诱导免疫耐受。iNKT细胞的激活需要与专职抗原呈递细胞相互作用，如树突状细胞（DCs）。我们研究了不同DC亚群调节iNKT细胞功能的能力。我们证明，用白细胞介素（IL）-10处理单核细胞来源的DC所产生的耐受性DC（tolDCs）可诱导人iNKT细胞的调节功能。与免疫原性DC相比，tolDCs诱导iNKT细胞增殖的能力降低，但这些细胞产生大量IL-10并获得无反应表型。这些无反应的Vα24(+) iNKT细胞能够在体外有效抑制同种异体CD4(+) T细胞增殖。此外，无反应的Vα24(+) iNKT细胞可在体外抑制DC成熟。我们得出结论，iNKT细胞与tolDCs的相互作用在免疫调节网络中起重要作用，这可能被用于治疗目的。
