Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea.
Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea.
Nat Commun. 2019 Feb 12;10(1):709. doi: 10.1038/s41467-019-08482-w.
T cells generate antigen-specific immune responses to their cognate antigen as a hallmark of adaptive immunity. Despite the importance of antigen-specific T cells, here we show that antigen non-related, bystander memory-like CD4 T cells also significantly contribute to autoimmune pathogenesis. Transcriptome analysis demonstrates that interleukin (IL)-1β- and IL-23-prime T cells that express pathogenic T17 signature genes such as RORγt, CCR6, and granulocyte macrophage colony-stimulating factor (GM-CSF). Importantly, when co-transferred with myelin-specific 2D2 TCR-transgenic naive T cells, unrelated OT-II TCR-transgenic memory-like T17 cells infiltrate the spinal cord and produce IL-17A, interferon (IFN)-γ, and GM-CSF, increasing the susceptibility of the recipients to experimental autoimmune encephalomyelitis in an IL-1 receptor-dependent manner. In humans, IL-1R1 memory CD4 T cells are major producers of IL-17A and IFN-γ in response to IL-1β and IL-23. Collectively, our findings reveal the innate-like pathogenic function of antigen non-related memory CD4 T cells, which contributes to the development of autoimmune diseases.
T 细胞针对其同源抗原产生抗原特异性免疫应答，这是适应性免疫的标志。尽管抗原特异性 T 细胞非常重要，但我们在这里表明，抗原非相关的旁观者记忆样 CD4 T 细胞也显著促进自身免疫发病机制。转录组分析表明，白细胞介素（IL）-1β 和 IL-23 可激活表达致病性 T17 特征基因（如 RORγt、CCR6 和粒细胞巨噬细胞集落刺激因子（GM-CSF）的 T 细胞。重要的是，当与髓鞘特异性 2D2 TCR 转基因幼稚 T 细胞共转导时，无关的 OT-II TCR 转基因记忆样 T17 细胞浸润脊髓并产生 IL-17A、干扰素（IFN）-γ 和 GM-CSF，以 IL-1 受体依赖的方式增加受体对实验性自身免疫性脑脊髓炎的易感性。在人类中，IL-1R1 记忆 CD4 T 细胞是对 IL-1β 和 IL-23 反应产生 IL-17A 和 IFN-γ 的主要细胞。总之，我们的发现揭示了抗原非相关记忆 CD4 T 细胞的先天样致病功能，这有助于自身免疫性疾病的发展。
