The University of Queensland Diamantina Institute, Immunology and Metabolic Medicine, Princess Alexandra Hospital, Woolloongabba, Queensland, Australia.
J Immunol. 2010 Feb 1;184(3):1242-50. doi: 10.4049/jimmunol.0902191. Epub 2009 Dec 18.
NKT cells can promote or inhibit adaptive immune responses. Cutaneous immunity is tightly regulated by cooperation between innate and adaptive immune processes, but the role of NKT cells in regulating cutaneous immunity is largely unknown. In this study, we show, in a mouse model, that skin-infiltrating CD1d-restricted NKT cells in HPV16-E7 transgenic hyperplastic skin produce IFN-gamma, which can prevent rejection of HPV16-E7-expressing skin grafts. Suppression of graft rejection is associated with the accumulation of CD1d(hi)-expressing CD11c(+)F4/80(hi) myeloid cells in hyperplastic skin. Blockade of CD1d, removal of NKT cells, or local inhibition of IFN-gamma signaling is sufficient to restore immune-mediated graft rejection. Thus, inhibition of NKT cell recruitment or function may enable effective immunity against tumor and viral Ags expressed in epithelial cells.
NKT 细胞可以促进或抑制适应性免疫反应。皮肤免疫受先天免疫和适应性免疫过程的紧密调节，但 NKT 细胞在调节皮肤免疫中的作用在很大程度上是未知的。在本研究中，我们在 HPV16-E7 转基因增生皮肤的小鼠模型中显示，皮肤浸润的 CD1d 限制性 NKT 细胞产生 IFN-γ，可防止 HPV16-E7 表达的皮肤移植物排斥。排斥抑制与增生皮肤中 CD1d(hi)表达的 CD11c(+)F4/80(hi)髓样细胞的积累有关。阻断 CD1d、去除 NKT 细胞或局部抑制 IFN-γ信号足以恢复免疫介导的移植物排斥。因此，抑制 NKT 细胞募集或功能可能使针对上皮细胞中表达的肿瘤和病毒抗原的有效免疫成为可能。
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