Hassan Ahmed, Heise Nico, Schimrock Anja, Willenzon Stefanie, Ravens Inga, Förster Reinhold, Georgiev Hristo
Institute of Immunology, Hannover Medical School, Hannover, Germany.
Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany.
Nat Commun. 2025 Jun 6;16(1):5274. doi: 10.1038/s41467-025-60617-4.
Peptide-specific PLZF innate-like T (PILT) cells are a member of the innate-like T cell family utilizing a diverse set of T cell receptor (TCR) Vβ chains. Yet there are no present studies providing clues into the developmental features of PILT cells at a transcriptome level. Here, we performed single-cell transcriptomic analyses of PILT cells and compared them to other members of the innate-like T cell family. We show that PILT cells share similar transcriptional profiles and overlapping developmental trajectories with invariant Natural Killer T (iNKT) cells. However, in contrast to iNKT cells, PILT cells display a polyclonal TCR repertoire closely resembling the one of conventional CD8 T cells, inferring MHC I restriction and a broader range of antigen specificity. We further show that artificial thymic organoid cultures (ATOC) support selection and development of PILT cells in vitro exhibiting similar transcriptional profiles to their counterparts maturing in the thymus. Moreover, using an "on-time" TCR retrogenic ATOC system, we provide evidence for an instructive role of TCR specificity in PILT cell lineage commitment and functional differentiation. Altogether, our findings provide further insights into the PILT cells unique characteristics and molecular mechanisms governing their development.
肽特异性PLZF天然样T（PILT）细胞是天然样T细胞家族的成员，利用多种T细胞受体（TCR）Vβ链。然而，目前尚无研究在转录组水平上为PILT细胞的发育特征提供线索。在此，我们对PILT细胞进行了单细胞转录组分析，并将其与天然样T细胞家族的其他成员进行了比较。我们发现PILT细胞与不变自然杀伤T（iNKT）细胞具有相似的转录谱和重叠的发育轨迹。然而，与iNKT细胞不同的是，PILT细胞显示出多克隆TCR库，与传统CD8 T细胞的TCR库非常相似，这意味着MHC I限制和更广泛的抗原特异性。我们进一步表明，人工胸腺类器官培养（ATOC）在体外支持PILT细胞的选择和发育，其转录谱与其在胸腺中成熟的对应细胞相似。此外，使用“适时”TCR逆转录ATOC系统，我们提供了TCR特异性在PILT细胞谱系定向和功能分化中起指导作用的证据。总之，我们的研究结果为PILT细胞的独特特征及其发育的分子机制提供了进一步的见解。
