Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada.
Immunology-Oncology Unit, Maisonneuve-Rosemont Hospital Research Center, Montréal, QC, Canada.
Immunol Cell Biol. 2022 Mar;100(3):205-217. doi: 10.1111/imcb.12520. Epub 2022 Jan 23.
Negative selection of developing T cells plays a significant role in T-cell tolerance to self-antigen. This process relies on thymic antigen-presenting cells which express both self-antigens and cosignaling molecules. Inducible T-cell costimulator (ICOS) belongs to the CD28 family of cosignaling molecules and binds to ICOS ligand (ICOSL). The ICOS signaling pathway plays important roles in shaping the immune response to infections, but its role in central tolerance is less well understood. Here we show that ICOSL is expressed by subsets of thymic dendritic cells and medullary thymic epithelial cells as well as thymic B cells. ICOS expression is upregulated as T cells mature in the thymus and correlates with T-cell receptor signal strength during thymic selection. We also provide evidence of a role for ICOS signaling in mediating negative selection. Our findings suggest that ICOS may fine-tune T-cell receptor signals during thymic selection contributing to the generation of a tolerant T-cell population.
负选择在 T 细胞发育过程中发挥着重要作用，可使 T 细胞对自身抗原产生耐受。这一过程依赖于表达自身抗原和共刺激分子的胸腺抗原呈递细胞。诱导性 T 细胞共刺激分子（ICOS）属于 CD28 家族的共刺激分子，与 ICOS 配体（ICOSL）结合。ICOS 信号通路在调节对感染的免疫反应中起着重要作用，但它在中枢耐受中的作用还不太清楚。在这里，我们发现 ICOSL 在胸腺树突状细胞和髓质胸腺上皮细胞以及胸腺 B 细胞亚群中表达。ICOS 的表达随着 T 细胞在胸腺中的成熟而上调，并与胸腺选择过程中 T 细胞受体信号强度相关。我们还提供了证据表明 ICOS 信号在介导阴性选择中发挥作用。我们的研究结果表明，ICOS 可能在胸腺选择过程中微调 T 细胞受体信号，有助于产生耐受的 T 细胞群体。
