Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
Nat Commun. 2020 Jul 6;11(1):3366. doi: 10.1038/s41467-020-17136-1.
CD4 T lymphocytes consist of naïve, antigen-specific memory, and memory-phenotype (MP) cell compartments at homeostasis. We recently showed that MP cells exert innate-like effector function during host defense, but whether MP CD4 T cells are functionally heterogeneous and, if so, what signals specify the differentiation of MP cell subpopulations under homeostatic conditions is still unclear. Here we characterize MP lymphocytes as consisting of T-bet, T-bet, and T-bet subsets, with innate, Th1-like effector activity exclusively associated with T-bet cells. We further show that the latter population depends on IL-12 produced by CD8α type 1 dendritic cells (DC1) for its differentiation. Finally, our data demonstrate that this tonic IL-12 production requires TLR-MyD88 signaling independent of foreign agonists, and is further enhanced by CD40-CD40L interactions between DC1 and CD4 T lymphocytes. We propose that optimal differentiation of T-bet MP lymphocytes at homeostasis is driven by self-recognition signals at both the DC and Tcell levels.
CD4 T 淋巴细胞在体内平衡时由幼稚、抗原特异性记忆和记忆表型 (MP) 细胞区室组成。我们最近表明，MP 细胞在宿主防御期间发挥类似先天的效应功能，但 MP CD4 T 细胞是否在功能上具有异质性，如果是，在体内平衡条件下哪些信号指定 MP 细胞亚群的分化仍然不清楚。在这里，我们将 MP 淋巴细胞描述为由 T-bet、T-bet 和 T-bet 亚群组成，具有先天的、Th1 样效应活性，仅与 T-bet 细胞有关。我们进一步表明，后者群体依赖于 CD8α 型 1 树突状细胞 (DC1) 产生的 IL-12 进行分化。最后，我们的数据表明，这种持续的 IL-12 产生需要 TLR-MyD88 信号，而不需要外来激动剂，并且 CD40-CD40L 相互作用在 DC1 和 CD4 T 淋巴细胞之间进一步增强。我们提出，在体内平衡时 T-bet MP 淋巴细胞的最佳分化是由 DC 和 T 细胞水平的自身识别信号驱动的。
