Effect of TCR signaling attenuation on Treg and Tconv repertoires and gene expression by using single cell sequencing

During development, strongly self-reactive T cells are deleted in the thymus, while moderately self-reactive T cells differentiate into Treg cells, and only slightly self-reactive T cells will mature into Tconv. To study the effect of TCR signaling attenuation on T cell repertoire development, we used a mouse model of rheumatoid arthritis which harbors a mutation that induces TCR signal attenuation (SKG). CD4T cells were isolated from the spleen of WT and SKG mice, and sorted into Treg and Tconv. Finally, single cell VDJ and mRNA sequencing were performed using 10x technology.在T细胞发育进程中，强自身反应性T细胞会在胸腺内发生克隆清除，中等自身反应性T细胞分化为调节性T细胞（Treg），仅弱自身反应性T细胞可成熟为常规T细胞（Tconv）。为探究T细胞受体（TCR）信号衰减对T细胞库（T cell repertoire）发育的影响，本研究使用了携带可诱导TCR信号衰减突变的类风湿关节炎小鼠模型（SKG）。研究人员从野生型（WT）与SKG小鼠的脾脏中分离CD4 T细胞，并分选为调节性T细胞（Treg）与常规T细胞（Tconv）。最终采用10x技术完成了单细胞VDJ与mRNA测序。