Klein Ludger, Petrozziello Elisabetta
Institute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Planegg-Martinsried, Germany.
Nat Rev Immunol. 2025 Jan;25(1):57-72. doi: 10.1038/s41577-024-01076-8. Epub 2024 Sep 18.
The extent of central T cell tolerance is determined by the diversity of self-antigens that developing thymocytes 'see' on thymic antigen-presenting cells (APCs). Here, focusing on insights from the past decade, we review the functional adaptations of medullary thymic epithelial cells, thymic dendritic cells and thymic B cells for the purpose of tolerance induction. Their distinct cellular characteristics range from unconventional phenomena, such as promiscuous gene expression or mimicry of peripheral cell types, to strategic positioning in distinct microenvironments and divergent propensities to preferentially access endogenous or exogenous antigen pools. We also discuss how 'tonic' inflammatory signals in the thymic microenvironment may extend the intrathymically visible 'self' to include autoantigens that are otherwise associated with highly immunogenic peripheral environments.
中枢T细胞耐受性的程度取决于发育中的胸腺细胞在胸腺抗原呈递细胞（APC）上“看到”的自身抗原的多样性。在此，我们聚焦过去十年的研究进展，综述髓质胸腺上皮细胞、胸腺树突状细胞和胸腺B细胞为诱导耐受性所进行的功能适应性变化。它们独特的细胞特征涵盖了从非常规现象，如混杂基因表达或对外周细胞类型的模拟，到在不同微环境中的战略定位以及优先获取内源性或外源性抗原库的不同倾向。我们还讨论了胸腺微环境中的“持续性”炎症信号如何将胸腺内可见的“自身”扩展至包括那些原本与高免疫原性外周环境相关的自身抗原。
