The thesis focuses on elucidating the role of autoreactive T cell responses in the pathology of systemic sclerosis (SSc) and other connective tissue diseases (CTDs). To overcome the challenge of detecting rare autoreactive T cells in tissue, a novel toolkit was developed combining PET imaging, single-cell multiomics, multiplex immunohistochemistry, and functional assays. This enabled the characterization of antigen-specific T cell responses in lymph nodes and affected tissues. The work reveals disease-specific roles of autoreactive T cells, with cytotoxic CD8⁺ T cells playing a dominant role in SSc pathology, contrasting with helper T cell–B cell interactions in Sjögren’s syndrome. Additionally, the thesis identifies a novel subset of TRAIL⁺ CD4⁺ T cells with immunoregulatory properties. These cells are enriched in SSc tissues and lymph nodes, where they suppress effector CD4+ T cell proliferation and may safeguard against CD4 driven amplification of humoral immune responses. A reduced presence of TRAIL+ CD4+ T-cells in SSc correlates with severe vascular complications, suggesting a protective role and potential as biomarkers of disease progression.
Theogiannis Papadimitriou, PharmD, MSc, is a biomedical scientist with a background in pharmacy and immunology. He earned his PharmD from the Aristotle University of Thessaloniki and completed an MSc in Biomedical Sciences (with distinction) at Radboud University Medical Center, supported by a full scholarship. Since 2020, he has been pursuing a PhD in Rheumatology and Medical Immunology at Radboudumc. His research focuses on antigen-specific immune responses in systemic sclerosis, applying advanced immunological tools such as PET-CT, single-cell multi-omics, and in vitro assays to study autoreactive lymphocytes. Currently, he holds a postdoctoral role leading translational efforts in early-phase clinical trials targeting pathogenic immune cells in systemic sclerosis. His work has led to national and international collaborations and has been recognized with several awards, including the EULAR Best Basic Science Award, NVLE Young Investigator Award, and multiple presentation and travel awards.