Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia.
Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
Cell Death Differ. 2019 Dec;26(12):2727-2739. doi: 10.1038/s41418-019-0331-8. Epub 2019 Apr 24.
The selection of αβ T cells in the thymus is punctuated by checkpoints at which thymocytes differentiate or undergo apoptosis. Wave 1 deletion is defined as apoptosis within nascent αβ T-cell antigen receptor (TCR)-signalled thymocytes that lack CCR7 expression. The antigen-presenting cell (APC) types that mediate wave 1 deletion are unclear. To measure wave 1 deletion, we compared the frequencies of TCRβ + CD5 + Helios + CCR7- cells in nascent thymocyte cohorts in mice with normal or defective apoptosis. This thymocyte population is small in mice lacking major histocompatibility complex (MHC) expression. The scale of wave 1 deletion was increased by transgenic expression of the self-reactive Yae62 TCRβ chain, was almost halved when haemopoietic APCs lacked MHC expression and, surprisingly, was unchanged when epithelial cells lacked MHC expression. These findings demonstrate efficiency, and some redundancy, in the APC types that mediate wave 1 deletion in the normal mouse thymus.
胸腺中αβ T 细胞的选择受到检查点的影响，这些检查点决定了胸腺细胞是分化还是凋亡。第 1 波删除是指在缺乏 CCR7 表达的新生αβ T 细胞抗原受体（TCR）信号的胸腺细胞中发生的凋亡。介导第 1 波删除的抗原呈递细胞（APC）类型尚不清楚。为了测量第 1 波删除，我们比较了正常或凋亡缺陷小鼠中新生胸腺细胞群中 TCRβ+CD5+Helios+CCR7-细胞的频率。在缺乏主要组织相容性复合体（MHC）表达的小鼠中，这种胸腺细胞群体很小。转基因表达自身反应性 Yae62 TCRβ 链增加了第 1 波删除的规模，当造血 APC 缺乏 MHC 表达时，几乎减半，而当上皮细胞缺乏 MHC 表达时，却没有变化。这些发现表明，在正常小鼠胸腺中，介导第 1 波删除的 APC 类型具有效率和一定程度的冗余性。
