Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455; and.
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
J Immunol. 2014 Jun 15;192(12):5490-8. doi: 10.4049/jimmunol.1400722. Epub 2014 May 9.
CD1d-reactive invariant NKT cells (iNKT) play a vital role in determining the characteristics of immune responses to infectious agents. Previous reports suggest that iNKT cell activation during infection can be: 1) solely driven by cytokines from innate immune cells, 2) require microbial Ag, or 3) require self-Ag. In this study, we examined the role of Ag receptor stimulation in iNKT cells during several bacterial and viral infections. To test for Ag receptor signaling, Nur77(gfp) BAC transgenic mice, which upregulate GFP in response to Ag receptor but not inflammatory signals, were analyzed. iNKT cells in the reporter mice infected with mouse CMV produced IFN-γ but did not upregulate GFP, consistent with their reported CD1d-independent activation. However, two bacteria known to produce lipid Ags for iNKT cells induced GFP expression and cytokine production. In contrast, although Salmonella typhimurium was proposed to induce the presentation of a self-lipid, iNKT cells produced IFN-γ but did not upregulate GFP postinfection in vivo. Even in CD1d-deficient hosts, iNKT cells were still able to produce IFN-γ after S. typhimurium infection. Furthermore, although it has been proposed that endogenous lipid presentation is a result of TLR stimulation of APCs, injection of different TLR agonists led to iNKT cell IFN-γ but not increased GFP expression. These data indicate that robust iNKT cell responses to bacteria, as well as viruses, can be obtained in the absence of antigenic stimulation.
CD1d 反应性不变自然杀伤 T 细胞（iNKT）在决定对感染因子的免疫反应特征方面发挥着重要作用。先前的报告表明，感染过程中 iNKT 细胞的激活可以：1）仅由先天免疫细胞的细胞因子驱动，2）需要微生物 Ag，或 3）需要自身 Ag。在这项研究中，我们研究了 Ag 受体刺激在几种细菌和病毒感染期间对 iNKT 细胞的作用。为了测试 Ag 受体信号，我们分析了 Nur77(gfp)BAC 转基因小鼠，该小鼠响应 Ag 受体而不是炎症信号而上调 GFP。感染小鼠 CMV 的报告小鼠中的 iNKT 细胞产生 IFN-γ，但未上调 GFP，这与它们报道的 CD1d 非依赖性激活一致。然而，两种已知产生用于 iNKT 细胞的脂质 Ag 的细菌诱导 GFP 表达和细胞因子产生。相比之下，尽管鼠伤寒沙门氏菌被提出诱导自身脂质的呈递，但在体内感染后，iNKT 细胞产生 IFN-γ但不上调 GFP。即使在缺乏 CD1d 的宿主中，iNKT 细胞在感染鼠伤寒沙门氏菌后仍能产生 IFN-γ。此外，尽管已经提出内源性脂质呈递是 TLR 刺激 APC 的结果，但不同 TLR 激动剂的注射导致 iNKT 细胞产生 IFN-γ但 GFP 表达没有增加。这些数据表明，在没有抗原刺激的情况下，细菌和病毒都可以引起 iNKT 细胞的强烈反应。
