Autoimmune regulator (Aire) deficiency results in reduced memory CD8+ T cells after Listeria monocytogenes infection in a murine model
Autoimmune regulator (Aire) deficiency results in reduced memory CD8+ T cells after Listeria monocytogenes infection in a murine model
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DOI：
10.1002/1873-3468.14696
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发表时间：
2023-07-18
期刊：
影响因子：
3.5
通讯作者：
Liu，Hongming
中科院分区：
文献类型：
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作者：
Feng，Yi;Yao，Shu;Liu，Hongming
自身免疫调节因子（AIRE）基因的纯合突变削弱了胸腺阴性选择的自身反应性T细胞，导致自身免疫性多内分泌病-念珠菌病-外胚层营养不良（APECED）。然而，AIRE如何调节T细胞对外来病原体的反应尚不清楚。在这里，我们观察到Aire - / -小鼠在感染重组单核细胞增生李斯特菌菌株后，与野生型小鼠相比，其原始CD8+T细胞明显减少，但记忆T细胞数量和保护功能明显减少。在过继性转移模型中，外源性同源CD8+T细胞转移到Aire - / -小鼠中也显示出记忆T细胞数量的减少，这表明胸腺外表达Aire -的细胞在形成或维持记忆T细胞方面发挥了重要作用。此外，利用骨髓嵌合模型，我们发现Aire在放射耐药细胞中表达，在维持记忆表型中起重要作用。这些结果为胸腺外腺抗原在T细胞对感染反应中的作用提供了重要的见解。
Homozygous mutations in the autoimmune regulator (AIRE) gene that cripple thymic negative selection of autoreactive T cells result in autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy (APECED). However, how AIRE regulates the T‐cell response against foreign pathogens is not well understood. Here, we observed comparable primary CD8+T cells but a markedly reduced memory T‐cell population and protective function in Aire−/−mice compared with wild‐type after infection with a strain of recombinantListeria monocytogenes. In adoptive transfer models, exogenous congenic CD8+T cells transferred into Aire−/−mice also showed a reduction in the memory T‐cell population, indicating an important role for extrathymic Aire‐expressing cells in shaping or sustaining memory T cells. Moreover, using a bone marrow chimeric model, we found that Aire expressed in radioresistant cells plays an important role in maintaining the memory phenotype. These results provide important insights into the role of extrathymic Aire in the T‐cell response to infection.