英国伦敦大学Daniel J. Pennington和葡萄牙里斯本大学Gina J. Fiala研究组合作发现，围产期胸腺来源表达cd8 αβ的γδ T细胞是先天性干扰素-γ（IFN-γ）的产生细胞，并在IL-7R-STAT5B诱导的肿瘤中扩增。2024年5月27日出版的《自然—免疫学》杂志发表了这一最新研究成果。

据介绍，γδT细胞产生免疫反应主要与IFN-γ的快速分泌有关。研究人员在围产期胸腺中发现了分泌先天性IFN-γ的γδ T细胞群，这些细胞表达CD8αβ异二聚体，并在感染和癌症临床前模型中扩增。CD8αβ⁺ γδ T细胞的最佳发育受低T细胞受体信号以及白细胞介素 (IL)-4和IL-7的调控。

在两种T细胞瘤小鼠模型中，IL-7R-STAT5B信号的过度激活或组成型表达，会促进胸腺和外周淋巴器官中CD8αβ⁺ γδ T细胞的过量累积，这与疾病发生相关。

同样，CD8αβ⁺ γδ T细胞也是人急性T细胞淋巴细胞白血病儿童患者的一个特有亚群。这项研究揭示了CD8αβ⁺ γδ T细胞正常和恶性发育的特征，这些细胞在生命早期就已富集，并有助于先天性 IFN-γ 反应对抗感染和癌症。

附：英文原文

Title: Perinatal thymic-derived CD8αβ-expressing γδ T cells are innate IFN-γ producers that expand in IL-7R–STAT5B-driven neoplasms

Author: Sumaria, Nital, Fiala, Gina J., Incio, Daniel, Curado-Avelar, Marta, Cachucho, Ana, Pinheiro, Rben, Wiesheu, Robert, Kimura, Shunsuke, Courtois, Lucien, Blankenhaus, Birte, Darrigues, Julie, Suske, Tobias, Almeida, Afonso R. M., Minguet, Susana, Asnafi, Vahid, Lhermitte, Ludovic, Mullighan, Charles G., Coffelt, Seth B., Moriggl, Richard, Barata, Joo T., Pennington, Daniel J., Silva-Santos, Bruno

Issue&Volume: 2024-05-27

Abstract: 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.

DOI: 10.1038/s41590-024-01855-4

Source: https://www.nature.com/articles/s41590-024-01855-4