Joannou Kevin, Golec Dominic P, Wang Haiguang, Henao-Caviedes Laura M, May Julia F, Kelly Rees G, Chan Rigel, Jameson Stephen C, Baldwin Troy A
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Cell Signaling and Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
J Immunol. 2022 May 1;208(9):2131-2140. doi: 10.4049/jimmunol.2100360. Epub 2022 Apr 8.
Several unique waves of γδ T cells are generated solely in the fetal/neonatal thymus, whereas additional γδ T cell subsets are generated in adults. One intriguing feature of γδ T cell development is the coordination of differentiation and acquisition of effector function within the fetal thymus; however, it is less clear whether this paradigm holds true in adult animals. In this study, we investigated the relationship between maturation and thymic export of adult-derived γδ thymocytes in mice. In the Rag2pGFP model, immature (CD24) γδ thymocytes expressed high levels of GFP whereas only a minority of mature (CD24) γδ thymocytes were GFP Similarly, most peripheral GFP γδ T cells were immature. Analysis of γδ recent thymic emigrants (RTEs) indicated that most γδ T cell RTEs were CD24 and GFP, and adoptive transfer experiments demonstrated that immature γδ thymocytes can mature outside the thymus. Mature γδ T cells largely did not recirculate to the thymus from the periphery; rather, a population of mature γδ thymocytes that produced IFN-γ or IL-17 remained resident in the thymus for at least 60 d. These data support the existence of two populations of γδ T cell RTEs in adult mice: a majority subset that is immature and matures in the periphery after thymic emigration, and a minority subset that completes maturation within the thymus prior to emigration. Additionally, we identified a heterogeneous population of resident γδ thymocytes of unknown functional importance. Collectively, these data shed light on the generation of the γδ T cell compartment in adult mice.
几波独特的γδ T细胞仅在胎儿/新生儿胸腺中产生,而其他γδ T细胞亚群则在成年个体中产生。γδ T细胞发育的一个有趣特征是在胎儿胸腺内分化与效应功能获得的协调;然而,在成年动物中这种模式是否成立尚不清楚。在本研究中,我们调查了成年小鼠中成年来源的γδ胸腺细胞成熟与胸腺输出之间的关系。在Rag2pGFP模型中,未成熟(CD24)的γδ胸腺细胞表达高水平的GFP,而只有少数成熟(CD24)的γδ胸腺细胞是GFP阳性。同样,大多数外周GFP阳性的γδ T细胞是未成熟的。对γδ近期胸腺迁出细胞(RTEs)的分析表明,大多数γδ T细胞RTEs是CD24阴性且GFP阳性,过继转移实验表明未成熟的γδ胸腺细胞可以在胸腺外成熟。成熟的γδ T细胞在很大程度上不会从外周再循环到胸腺;相反,一群产生IFN-γ或IL-17的成熟γδ胸腺细胞在胸腺中停留至少60天。这些数据支持成年小鼠中存在两类γδ T细胞RTEs:一个主要亚群是未成熟的,在胸腺迁出后在外周成熟,另一个少数亚群在迁出前在胸腺内完成成熟。此外,我们鉴定出了一群功能重要性未知的驻留γδ胸腺细胞异质性群体。总的来说,这些数据揭示了成年小鼠γδ T细胞区室的产生情况。