2021, Immunology. DOI: 10.1111/imm.13441
Double‐negative T cells: Setting the stage for disease control or progression
Teresiama Velikkakam, Kenneth J. Gollob, Walderez Ornelas Dutra
Abstract Double‐negative (DN) T cells are present at relatively low frequencies in human peripheral blood, and are characterized as expressing the alpha‐beta or gamma‐delta T‐cell receptor (TCR), but not the CD4 nor the CD8 co‐receptors. Despite their low frequencies, these cells are potent producers of cytokines and, thus, are key orchestrators of immune responses. DN T cells were initially associated with induction of peripheral immunological tolerance and immunomodulatory activities related to disease prevention. However, other studies demonstrated that these cells can also display effector functions associated with pathology development. This apparent contradiction highlighted the heterogeneity of the DN T‐cell population. Here, we review phenotypic and functional characteristics of DN T cells, emphasizing their role in human diseases. The need for developing biomarkers to facilitate the translation of studies from animal models to humans will also be discussed. Finally, we will examine DN T cells as promising therapeutic targets to prevent or inhibit human disease development.
#paper https://doi.org/10.1111/imm.13441 Velikkakam, T, Gollob, KJ, and Dutra, WO. Double-negative T cells: setting the stage for disease control or progression. Immunology. (2022) 165:371–85. 这篇文献是关于双阴性T细胞DNT的综述文章。DNT是一群独特的T细胞，缺乏CD4和CD8辅助受体，但表达αβ TCR或γδ TCR，在人外周血中占比较低。DNT细胞能有效产生细胞因子，是免疫反应的关键协调者。1.DNT从哪里来？DNT 的确切来源仍有很多盲点，有研究表明DNT细胞可以源自胸腺和外周环境。外周血中DNT细胞可以通过可能逃避胸腺中的负选择以及随后在外周中的激活和扩增。另外，体外也可诱导产生DNT细胞。2.DNT亚群：存在高度异质性，未有正式定义，来源不同研究课题，如初始nDNT和激活态aDNT。3.DNT与疾病：它是多种人类疾病的发病机制的主角，特别是自身免疫疾病、炎症性疾病和移植。其调节功能损害了必要的炎症效应机制，或者介导细胞死亡和组织破坏。多数文献DNT研究源自小鼠模型，许多是转基因的。人类DNT会有所区别，还是需要系统的梳理DNT细胞的功能和在疾病中的作用。