Department of Physiology, McGill University, Montreal, QC, Canada; McGill University Research Centre on Complex Traits, Montreal, QC, Canada.
Immunology-Oncology Unit, Maisonneuve-Rosemont Hospital Research Center, Montreal, QC, Canada; Department of Microbiology, Immunology, and Infectious Disease, Université de Montréal, Montreal, QC, Canada.
Cell Rep. 2021 Nov 30;37(9):110064. doi: 10.1016/j.celrep.2021.110064.
CD4 T cells have a remarkable potential to differentiate into diverse effector lineages following activation. Here, we probe the heterogeneity present among naive CD4 T cells before encountering their cognate antigen to ask whether their effector potential is modulated by pre-existing transcriptional and chromatin landscape differences. Single-cell RNA sequencing shows that key drivers of variability are genes involved in T cell receptor (TCR) signaling. Using CD5 expression as a readout of the strength of tonic TCR interactions with self-peptide MHC, and sorting on the ends of this self-reactivity spectrum, we find that pre-existing transcriptional differences among naive CD4 T cells impact follicular helper T (T) cell versus non-T effector lineage choice. Moreover, our data implicate TCR signal strength during thymic development in establishing differences in naive CD4 T cell chromatin landscapes that ultimately shape their effector potential.
CD4 T 细胞在激活后具有分化为多种效应谱系的惊人潜力。在这里，我们在遇到同源抗原之前探测幼稚 CD4 T 细胞中的异质性，以了解它们的效应潜能是否受到预先存在的转录和染色质景观差异的调节。单细胞 RNA 测序表明，变异性的关键驱动因素是涉及 T 细胞受体 (TCR) 信号的基因。使用 CD5 表达作为 T 细胞受体 (TCR) 与自身肽 MHC 持续相互作用强度的读出值，并在这个自我反应谱的两端进行分选，我们发现幼稚 CD4 T 细胞中的预先存在的转录差异影响滤泡辅助 T (Tfh) 细胞与非-T 效应谱系的选择。此外，我们的数据表明，胸腺发育过程中的 TCR 信号强度在建立幼稚 CD4 T 细胞染色质景观差异方面发挥了作用，而这些差异最终决定了它们的效应潜能。
