瑞典卡罗林斯卡大学附属医院Taras Kreslavsky研究团队发现，胸腺先天性类T细胞具有的炎症相关自身抗原可诱导自身反应性CD8⁺胸腺细胞的清除。2024年7月11日出版的《自然-免疫学》发表了这项成果。

研究人员发现CD8⁺ T细胞对T细胞衍生的炎症相关自身抗原的耐受性，是在胸腺中有效诱导产生的，并获得了表达这些分子的冗余细胞支持。除胸腺上皮细胞外，还包括胸腺嗜酸性粒细胞和先天性类T细胞，这些细胞主要表达所有活化T细胞亚群的特征分子。

该研究表明，微量的先天性类T细胞诱导的T细胞直接抗原呈递足以清除自反应性CD8⁺胸腺细胞。对这种效应分子的耐受性至关重要，因为胸腺中与炎症相关单一自身抗原的减少会破坏这种耐受性，从而导致整个效应T细胞亚群的自身免疫性缺失。

据了解，诱导炎症反应的各种自抗原的上调与病原体衍生的外来抗原的出现，会在空间和时间上发生重叠。因此，区分这些炎症相关自抗原和病原体衍生分子，是适应性免疫系统面临的一项独特挑战。

附：英文原文

Title: Direct presentation of inflammation-associated self-antigens by thymic innate-like T cells induces elimination of autoreactive CD8+ thymocytes

Author: You, Yuanyuan, Dunst, Josefine, Ye, Kewei, Sandoz, Patrick A., Reinhardt, Annika, Sandrock, Inga, Comet, Natalia R., Sarkar, Rupak Dey, Yang, Emily, Duprez, Estelle, Agudo, Judith, Brown, Brian D., Utz, Paul J., Kastenmller, Wolfgang, Gerlach, Carmen, Prinz, Immo, nfelt, Bjrn, Kreslavsky, Taras

Issue&Volume: 2024-07-11

Abstract: Upregulation of diverse self-antigens that constitute components of the inflammatory response overlaps spatially and temporally with the emergence of pathogen-derived foreign antigens. Therefore, discrimination between these inflammation-associated self-antigens and pathogen-derived molecules represents a unique challenge for the adaptive immune system. Here, we demonstrate that CD8+ T cell tolerance to T cell-derived inflammation-associated self-antigens is efficiently induced in the thymus and supported by redundancy in cell types expressing these molecules. In addition to thymic epithelial cells, this included thymic eosinophils and innate-like T cells, a population that expressed molecules characteristic for all major activated T cell subsets. We show that direct T cell-to-T cell antigen presentation by minute numbers of innate-like T cells was sufficient to eliminate autoreactive CD8+ thymocytes. Tolerance to such effector molecules was of critical importance, as its breach caused by decreased thymic abundance of a single model inflammation-associated self-antigen resulted in autoimmune elimination of an entire class of effector T cells.

DOI: 10.1038/s41590-024-01899-6

Source: https://www.nature.com/articles/s41590-024-01899-6