Svensson Mattias, Zubairi Soombul, Maroof Asher, Kazi Fatima, Taniguchi Masaru, Kaye Paul M
Immunology and Infection Unit, Department of Biology, University of York, Heslington, York YO10 5YW, United Kingdom.
Infect Immun. 2005 Nov;73(11):7541-7. doi: 10.1128/IAI.73.11.7541-7547.2005.
Gamma interferon (IFN-gamma)-regulated chemokines of the CXC family have been implicated as key regulators of a variety of T-cell-dependent inflammatory processes. However, the cellular source(s) of IFN-gamma that regulates their early expression has rarely been defined. Here, we have directly addressed this question in mice after Leishmania donovani infection. Comparison of CXCL10 mRNA accumulation in normal and IFN-gamma-deficient mice confirmed an absolute requirement for IFN-gamma for sustained (24 h) expression of CXCL10 mRNA accumulation in this model. In normal mice, IFN-gamma was produced by both CD3int NK1.1+ NKT cells and CD3- NK1.1+ NK cells, as detected by intracellular flow cytometry. Strikingly, B6.Jalpha281-/- mice lacking NKT cells that express the invariant Valpha14Jalpha18 T-cell-receptor alpha chain, although retaining a significant population of IFN-gamma-producing NK cells and NKT cells, were unable to sustain CXCL10 mRNA accumulation. These data indicate that invariant NKT cells are indispensable for the regulation of hepatic CXCL10 gene expression during L. donovani infection.
CXC家族中受γ干扰素（IFN-γ）调节的趋化因子被认为是多种T细胞依赖性炎症过程的关键调节因子。然而，调节其早期表达的IFN-γ的细胞来源很少被明确。在此，我们在杜氏利什曼原虫感染后的小鼠中直接解决了这个问题。正常小鼠和IFN-γ缺陷小鼠中CXCL10 mRNA积累的比较证实，在该模型中持续（24小时）表达CXCL10 mRNA积累绝对需要IFN-γ。通过细胞内流式细胞术检测，在正常小鼠中，CD3int NK1.1 + NKT细胞和CD3 - NK1.1 + NK细胞均可产生IFN-γ。令人惊讶的是，缺乏表达恒定Valpha14Jalpha18 T细胞受体α链的NKT细胞的B6.Jalpha281 - / - 小鼠，尽管保留了大量产生IFN-γ的NK细胞和NKT细胞，但仍无法维持CXCL10 mRNA的积累。这些数据表明，恒定NKT细胞对于杜氏利什曼原虫感染期间肝脏CXCL10基因表达的调节是必不可少的。
