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永久剂，这是几种自身免疫性疾病的基础。 Pemphigus的发病机理在很大程度上取决于由B细胞/浆细胞形成的IgG自身抗体，这些自身抗体需要自身反应性T淋巴细胞的帮助。在Pegasus的第一个资金期间，我们建立了旨在鉴定针对Desmoglein 3（DSG3）的旨在识别外周血T细胞反应（DSG3），这是Pemphigus vulgaris的主要自动抗原。此外，我们设法检测到Pemphigus患者血液中DSG3小肽成分特有的T细胞。这些DSG3肽特别感兴趣，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。我们遇到了新的技术，包括ELISPOT分析和葡萄晶染色，以检测DSG3肽特异性T细胞。现在，我们想完善这些技术，还可以在疾病的不同阶段和不同的治疗方案下监测DSG3反应性T细胞子集的存在。此外，我们计划研究其他免疫细胞，例如DSG3反应性B细胞，在很大程度上取决于T细胞的激活以及促炎和抗炎因子，这些因素可能有助于Pemphigus发病机理，这些发现希望在PV中更特定的治疗标记，并可以更好地了解PEM中的PEM源中的受到独特的免疫原理的参与。