Development of New Immunotherapy for Oral Cancer Using Dendritic Cells

自然杀伤T（NKT）细胞在被合成的CD 1d配体α-半乳糖神经酰胺（α-GalCer）通过其不变的Vα14受体刺激后产生大量与Th 1应答（IFN-γ）和Th 2应答（IL-4）相关的细胞因子。然而，粘附或共刺激分子在α-GalCer激活NKT细胞中所起的作用仍不清楚。为了解决这一问题，使用LFA-1^+和CD 28 ^+小鼠研究α-GalCer刺激后NKT细胞产生IL-4和IFN-γ的情况。LFA-1^+小鼠表现出对体外和体内极化Th 2型应答的IL-4产生增加，表现为B细胞活化和血清IgE升高。相反，在CD 28 ^+小鼠中，IL-4和IFN-γ的产生受损，导致Th 2型应答严重丧失，表现为血清IgE消失。这些结果表明，LFA-1粘附受体和CD 28共刺激受体选择性地调节α-GalCer激活的NKT细胞的Th 1和Th 2样功能。

Natural killer T (NKT) cells produce large amounts of cytokines associated with both the Th1 response (IFN-γ) and Th2 response (IL-4) after being stimulated by the synthetic CD1d ligand α-galactosylceramide (α-GalCer) by their invariant Vα14 receptor. However, the role played by adhesion or co-stimulation molecules in the activation of NKT cells by α-GalCer remains unclear. To address this issue, LFA-1^+ and CD28^+ mice were used to investigate IL-4 and IFN-γ production by NKT cells following α-GalCer stimulation. LFA-1^+ mice showed increased IL-4 production in response to in vitro and in vivo polarized Th2-type responses, represented by activation of B cells and serum IgE elevation. In contrast, impairment of production of IL-4 and IFN-γ in CD28^+ mice resulted in a profound inability to polarize the Th2-type response, represented by the abolishment of serum IgE. These results imply that the LFA-1 adhesion receptor and the CD28 co-stimulatory receptor selectively regulate Th1- and Th2-like functions of α-GalCer-activated NKT cells.