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

T淋巴细胞被认为是自身免疫反应的关键启动者和永久者，而自身免疫反应是几种自身免疫性疾病的基础。天疱疮的发病机制在很大程度上依赖于B细胞/浆细胞形成的免疫球蛋白抗体，这种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，我们已经建立了多项体外试验，目的是鉴定外周血T细胞对寻常型天疱疮的主要自身抗原--桥粒芯糖蛋白3(Dsg3)的反应。此外，我们设法在天疱疮患者的血液中检测到Dsg3小肽成分的特异性T细胞。这些Dsg3多肽特别令人感兴趣，因为它们可以在耐受性条件下应用，以恢复对Dsg3的免疫耐受。我们遇到了新的技术，包括ELISPOT分析和葡聚糖染色来检测Dsg3肽特异性T细胞。我们现在想改进这些技术，以便在疾病的不同阶段和不同的治疗方案下也监测Dsg3反应性T细胞亚群的存在。此外，我们计划研究更多的免疫细胞，如Dsg3反应性B细胞，它们主要依赖于T细胞的激活，以及可能参与天疱疮发病的促炎和抗炎因子，这些发现有望成为天疱疮更特异的治疗标志物，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。

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.