Wilson Michael T, Johansson Cecilia, Olivares-Villagómez Danyvid, Singh Avneesh K, Stanic Aleksandar K, Wang Chyung-Ru, Joyce Sebastian, Wick Mary Jo, Van Kaer Luc
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10913-8. doi: 10.1073/pnas.1833166100. Epub 2003 Sep 5.
CD1d-restricted natural killer T (NKT) cells are a subset of regulatory T cells that react with glycolipid antigens. Although preclinical studies have effectively targeted NKT cells for immunotherapy, little is known regarding the early in vivo response of these cells to antigenic stimulation. We have analyzed the early response of NKT cells to glycolipid antigens and bacterial infection by using specific reagents for tracking these cells. Our results demonstrate dramatic in vivo expansion and surface phenotype alterations after NKT cell activation with alpha-galactosylceramide. In addition, we show significant NK1.1 down-modulation on NKT cells in the setting of oral Salmonella infection. Our results indicate that in vivo activation of NKT cells leads to a dynamic response characterized by surface receptor down-modulation and expansion. These findings alter current understanding of NKT cell biology and should aid in the rational design of NKT cell-based immunotherapies.
CD1d 限制性自然杀伤 T（NKT）细胞是一类可与糖脂抗原发生反应的调节性 T 细胞亚群。尽管临床前研究已有效地将 NKT 细胞作为免疫治疗的靶点，但对于这些细胞在体内对抗原刺激的早期反应却知之甚少。我们通过使用追踪这些细胞的特异性试剂，分析了 NKT 细胞对糖脂抗原和细菌感染的早期反应。我们的结果表明，用α-半乳糖神经酰胺激活 NKT 细胞后，其在体内会发生显著扩增以及表面表型改变。此外，我们发现在口服沙门氏菌感染的情况下，NKT 细胞上的 NK1.1 会明显下调。我们的结果表明，NKT 细胞在体内的激活会导致一种以表面受体下调和扩增为特征的动态反应。这些发现改变了当前对 NKT 细胞生物学的认识，并应有助于基于 NKT 细胞的免疫疗法的合理设计。
