During mammalian T cell development, CD4⁺CD8⁺ double-positive (DP) thymocytes must make a lineage choice to become either conventional CD4⁺ or CD8⁺ T cells, dependent on their specificity for MHC-II or MHC-I, respectively. Alternatively, DP thymocytes can decide to become innate-like T cells in response to nonclassical MHC-I molecules. A key feature is the downregulation of CD8, which causes transient T cell receptor (TCR) signaling in MHC-I-selected DP thymocytes. Hence, this kinetic signaling model postulates that short or long duration of TCR signals during positive selection can direct the development of cytotoxic or helper T cell lineages. In this opinion article, we discuss the effects of constitutive expression of transgenic CD8 and prolonged TCR signaling on T cell lineage choice in MHC-I selected mouse thymocytes.

在哺乳动物T细胞发育过程中，CD4 ⁺ CD8 ⁺双阳性（DP）胸腺细胞必须做出血统选择，才能成为常规CD4 ⁺或CD8 ⁺T细胞分别取决于其对MHC-II或MHC-1的特异性。或者，DP胸腺细胞可以响应非经典的MHC-1分子而决定成为先天性T细胞。一个关键特征是CD8的下调，这会在MHC-1选择的DP胸腺细胞中引起瞬时T细胞受体（TCR）信号传导。因此，该动力学信号模型假定在阳性选择期间TCR信号的持续时间短或长可以指导细胞毒性或辅助性T细胞谱系的发展。在这篇观点文章中，我们讨论了转基因CD8的组成型表达和延长的TCR信号转导对MHC-1选择的小鼠胸腺细胞中T细胞谱系选择的影响。