围产期胸腺来源的表达 CD8αβ 的 γδ T 细胞是先天的 IFN-γ 产生者，可在 IL-7R-STAT5B 驱动的肿瘤中扩增。
Perinatal thymic-derived CD8αβ-expressing γδ T cells are innate IFN-γ producers that expand in IL-7R-STAT5B-driven neoplasms.
发表日期：2024 May 27
作者：
Nital Sumaria, Gina J Fiala, Daniel Inácio, Marta Curado-Avelar, Ana Cachucho, Rúben Pinheiro, Robert Wiesheu, Shunsuke Kimura, Lucien Courtois, Birte Blankenhaus, Julie Darrigues, Tobias Suske, Afonso R M Almeida, Susana Minguet, Vahid Asnafi, Ludovic Lhermitte, Charles G Mullighan, Seth B Coffelt, Richard Moriggl, João T Barata, Daniel J Pennington, Bruno Silva-Santos
来源：
NATURE IMMUNOLOGY
摘要：
γδ T 细胞对免疫反应的贡献与干扰素-γ (IFN-γ) 的快速分泌有关。在这里，我们展示了先天产生 IFN-γ 的 γδ T 细胞的围产期胸腺波，这些细胞表达 CD8αβ 异二聚体，并在感染和癌症的临床前模型中扩增。最佳 CD8αβ γδ T 细胞发育由低 T 细胞受体信号传导和白细胞介素 (IL)-4 和 IL-7 的提供引导。该群体与病理相关，因为在两种 T 细胞瘤形成小鼠模型中，过度活跃或组成型 IL-7R-STAT5B 信号传导促进 CD8αβ γδ T 细胞在胸腺和外周淋巴器官中超生理积累。同样，CD8αβ γδ T 细胞定义了人类 T 细胞急性淋巴细胞白血病儿科患者的一个独特亚群。这项工作描述了 CD8αβ γδ T 细胞的正常和恶性发育，这些细胞在生命早期富集，有助于对感染和癌症的先天 IFN-γ 反应。© 2024。作者。
The contribution of γδ T cells to immune responses is associated with rapid secretion of interferon-γ (IFN-γ). Here, we show a perinatal thymic wave of innate IFN-γ-producing γδ T cells that express CD8αβ heterodimers and expand in preclinical models of infection and cancer. Optimal CD8αβ+ γδ T cell development is directed by low T cell receptor signaling and through provision of interleukin (IL)-4 and IL-7. This population is pathologically relevant as overactive, or constitutive, IL-7R-STAT5B signaling promotes a supraphysiological accumulation of CD8αβ+ γδ T cells in the thymus and peripheral lymphoid organs in two mouse models of T cell neoplasia. Likewise, CD8αβ+ γδ T cells define a distinct subset of human T cell acute lymphoblastic leukemia pediatric patients. This work characterizes the normal and malignant development of CD8αβ+ γδ T cells that are enriched in early life and contribute to innate IFN-γ responses to infection and cancer.© 2024. The Author(s).