Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, Netherlands.
Division of Immunology, Paul-Ehrlich-Institut, IMG53, Langen, Germany.
Sci Adv. 2024 Jul 26;10(30):eadl0796. doi: 10.1126/sciadv.adl0796. Epub 2024 Jul 24.
Naive T cells recirculate between the spleen and lymph nodes where they mount immune responses when meeting dendritic cells presenting foreign antigen. As this may happen anywhere, naive T cells ought to visit all lymph nodes. Here, deep sequencing almost-complete TCR repertoires led to a comparison of different lymph nodes within and between individual mice. We find strong evidence for a deterministic CD4/CD8 lineage choice and a consistent spatial structure. Specifically, some T cells show a preference for one or multiple lymph nodes, suggesting that their TCR interacts with locally presented (self-)peptides. These findings are mirrored in TCR-transgenic mice showing localized CD69 expression, retention, and cell division. Thus, naive T cells intermittently sense antigenically dissimilar niches, which is expected to affect their homeostatic competition.
幼稚 T 细胞在脾脏和淋巴结之间循环，当遇到呈递外来抗原的树突状细胞时，它们会引发免疫反应。由于这种情况可能发生在任何地方，幼稚 T 细胞应该访问所有的淋巴结。在这里，深度测序几乎完整的 TCR 库导致了对个体小鼠内和小鼠之间不同淋巴结的比较。我们发现强有力的证据表明 CD4/CD8 谱系选择是确定的，并且存在一致的空间结构。具体来说，一些 T 细胞表现出对一个或多个淋巴结的偏好，这表明它们的 TCR 与局部呈递的（自身）肽相互作用。在显示局部 CD69 表达、保留和细胞分裂的 TCR 转基因小鼠中也观察到了这些发现。因此，幼稚 T 细胞间歇性地感知抗原性不同的小生境，这预计会影响它们的稳态竞争。
