Monitoring of autoreactive T cells responses in active and remittent pemphigus vulgaris

监测活动性和缓解性寻常型天疱疮的自身反应性 T 细胞反应

• 批准号: 319340680
• 负责人: Professor Dr. Michael Hertl
• 金额: --
• 依托单位: Klinik für Dermatologie und Allergologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/319340680?language=en
• 关键词: Monitoring; autoreactive; cells; responses; active

T lymphocytes are considered to be critical initiators and perpetuators of autoimmune responses which are the basis for several autoimmune disorders. The pathogenesis of pemphigus largely depends on IgG autoantibodies which are formed by B cells/plasma cells which require help from autoreactive T-lymphocytes. In the 1st funding period of PEGASUS, we have established seral ex vivo assays aimed at identifying peripheral blood T cell responses against desmoglein 3 (Dsg3), the major autoantigen of pemphigus vulgaris. In addition, we managed to detect T-cells specific for small peptide components of Dsg3 in the blood of pemphigus patients. These Dsg3 peptides are of particular interest because they can be applied under tolerogenic conditions to restore immune tolerance against Dsg3. We have encountered novel technologies including ELISPOT analysis and dextramer staining to detect Dsg3 peptide-specific T cells. We now want to refine these techniques to also monitor the presence of Dsg3 reactive T cell subsets at different stages of the disease and under different therapeutic regimens. In addition, we plan to study additional immune cells, such as Dsg3-reactive B cells which largely depend on T cell activation and pro- and anti-inflammatory factors which may contribute to the pemphigus pathogenesis, These finding will hopefully be more specific therapeutic markers in PV and may contribute to a better understanding of the involvement of distinct immune cells in the pathogenesis of pemphigus.

T 淋巴细胞被认为是自身免疫反应的关键启动者和持续者，而自身免疫反应是多种自身免疫性疾病的基础。天疱疮的发病机制很大程度上取决于B细胞/浆细胞形成的IgG自身抗体，需要自身反应性T淋巴细胞的帮助。在 PEGASUS 的第一个资助期，我们建立了一系列离体检测，旨在识别外周血 T 细胞针对桥粒芯糖蛋白 3 (Dsg3)（寻常型天疱疮的主要自身抗原）的反应。此外，我们还成功在天疱疮患者的血液中检测到对 Dsg3 小肽成分具有特异性的 T 细胞。这些 Dsg3 肽特别令人感兴趣，因为它们可以在耐受性条件下应用以恢复针对 Dsg3 的免疫耐受性。我们遇到了新技术，包括 ELISPOT 分析和右旋聚体染色来检测 Dsg3 肽特异性 T 细胞。我们现在希望改进这些技术，以监测 Dsg3 反应性 T 细胞亚群在疾病不同阶段和不同治疗方案下的存在。此外，我们计划研究其他免疫细胞，例如 Dsg3 反应性 B 细胞，其很大程度上依赖于 T 细胞激活以及可能有助于天疱疮发病机制的促炎和抗炎因子。这些发现有望成为 PV 中更特异的治疗标志物，并可能有助于更好地了解不同免疫细胞在天疱疮发病机制中的参与。