Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, Jilin, China; National-local Joint Engineering Laboratory of Animal Models for Human Diseases, Changchun, China.
Department of Pediatric Surgery, The First Hospital of Jilin University, Changchun, China.
Immunol Lett. 2024 Jun;267:106861. doi: 10.1016/j.imlet.2024.106861. Epub 2024 Apr 30.
Hematopoietic precursors (HPCs) entering into the thymus undergo a sequential process leading to the generation of a variety of T cell subsets. This developmental odyssey unfolds in distinct stages within the thymic cortex and medulla, shaping the landscape of T cell receptor (TCR) expression and guiding thymocytes through positive and negative selection. Initially, early thymic progenitors (ETPs) take residence in the thymic cortex, where thymocytes begin to express their TCR and undergo positive selection. Subsequently, thymocytes transition to the thymic medulla, where they undergo negative selection. Both murine and human thymocyte development can be broadly classified into distinct stages based on the expression of CD4 and CD8 coreceptors, resulting in categorizations as double negative (DN), double positive (DP) or single positive (SP) cells. Thymocyte migration to the appropriate thymic microenvironment at the right differentiation stage is pivotal for the development and the proper functioning of T cells, which is critical for adaptive immune responses. The journey of lymphoid progenitor cells into the T cell developmental pathway hinges on an ongoing dialogue between the differentiating cell and the signals emanating from the thymus niche. Herein, we review the contribution of the key factors mentioned above for the localization, migration and emigration of thymocytes.
造血前体细胞(HPCs)进入胸腺后,会经历一个连续的过程,最终产生多种 T 细胞亚群。这一发育历程在胸腺皮质和髓质的不同阶段展开,塑造了 T 细胞受体(TCR)表达的格局,并指导胸腺细胞通过阳性选择和阴性选择。最初,早期胸腺祖细胞(ETP)定居在胸腺皮质,在此处胸腺细胞开始表达 TCR 并经历阳性选择。随后,胸腺细胞迁移到胸腺髓质,在那里经历阴性选择。基于 CD4 和 CD8 核心受体的表达,鼠类和人类的胸腺细胞发育都可以大致分为不同的阶段,从而分为双阴性(DN)、双阳性(DP)或单阳性(SP)细胞。胸腺细胞在适当的分化阶段迁移到适当的胸腺微环境对于 T 细胞的发育和正常功能至关重要,这对于适应性免疫反应至关重要。淋巴祖细胞进入 T 细胞发育途径的旅程取决于分化细胞与胸腺龛位发出的信号之间的持续对话。在此,我们综述了上述关键因素对胸腺细胞定位、迁移和迁出的贡献。