Invariant NKT (iNKT) cells are an innate-like population characterized by their recognition of glycolipid Ags and rapid cytokine production upon activation. Unlike conventional T cells, which require TCR ligation, iNKT cells can also be stimulated independently of their TCR. This feature allows iNKT cells to respond even in the absence of glycolipid Ags, for example, during viral infections. Although the TCR-dependent and -independent activation of iNKT cells have been relatively well established, the exact contributions of IL-12, IL-18, and TLRs remain unclear for these two activation pathways. To definitively investigate how these components affect the direct and indirect stimulation of iNKT cells, we used mice deficient for either MyD88 or the IL-12Rβ2 in the T cell lineage. Using these tools, we demonstrate that IL-12, IL-18, and TLRs are completely dispensable for the TCR activation pathway when a strong agonist is used. In contrast, during murine CMV infection, when the TCR is not engaged, IL-12 signaling is essential, and TLR signaling is expendable. Importantly, to our knowledge, we discovered an intrinsic requirement for IL-18 signaling by splenic iNKT cells but not liver iNKT cells, suggesting that there might be diversity, even within the NKT1 population.

中文翻译：

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在抗原依赖性和抗原非依赖性激活期间，不变的 NKT 细胞反应具有不同的信号传导要求

不变 NKT (iNKT) 细胞是一种先天性细胞群，其特征在于它们识别糖脂 Ags 并在激活后快速产生细胞因子。与需要 TCR 连接的传统 T 细胞不同，iNKT 细胞也可以独立于它们的 TCR 进行刺激。这一特性使 iNKT 细胞即使在没有糖脂抗原的情况下也能做出反应，例如在病毒感染期间。尽管 iNKT 细胞的 TCR 依赖性和非依赖性激活已经相对完善，但 IL-12、IL-18 和 TLR 对这两种激活途径的确切贡献仍不清楚。为了明确研究这些成分如何影响 iNKT 细胞的直接和间接刺激，我们使用了 T 细胞谱系中缺乏 MyD88 或 IL-12Rβ2 的小鼠。使用这些工具，我们证明 IL-12、IL-18、当使用强激动剂时，TLR 对于 TCR 激活途径来说是完全可有可无的。相比之下，在鼠 CMV 感染期间，当 TCR 不参与时，IL-12 信号是必不可少的，而 TLR 信号是消耗性的。重要的是，据我们所知，我们发现了脾 iNKT 细胞而非肝脏 iNKT 细胞对 IL-18 信号传导的内在需求，这表明即使在 NKT1 群体中也可能存在多样性。