Quantitative evaluation of T-cell repertoire restoration following hematopoietic stem cell transplantation in patients with and without graft versus host disease

Introduction: Acute graft-versus-host disease (aGVHD) is a major cause of mortality following hematopoietic stem cell transplantation (HSCT). Its pathogenesis is primarily driven by alloimmune T cells, which recognize host tissues as foreign. A deeper characterization of the T cell receptor (TCR) repertoires in patients with aGVHD could provide critical insights into the disease's mechanisms and identify potential predictive biomarkers. Methods: We employed next-generation sequencing to comprehensively profile the T cell receptor alpha (TRA) and beta (TRB) chains in HSCT recipients, comparing those with and without aGVHD. Our analysis focused on defining the functional kinetics of TCR clones, monitoring changes in overall T-cell diversity through the identification of complementarity-determining region 3 (CDR3) sequences, and quantifying the extent of clonal expansion within the T-cell population. Results: Our analysis revealed that TCR repertoires exhibited significantly increased diversity in patients with active aGVHD compared to those without. Notably, this elevated diversity was dynamic and decreased as the symptoms of aGVHD improved clinically. Furthermore, TCR clustering analysis identified the presence of common TCR repertoire signatures among different patients who developed aGVHD, suggesting shared antigen-driven T cell responses. Discussion: The dynamic changes and shared signatures within the TCR repertoire are closely associated with the development and resolution of aGVHD. These findings indicate that monitoring the TCR repertoire could serve as a valuable tool for predicting the onset of aGVHD. This approach holds promise for facilitating more personalized diagnostic and treatment strategies for aGVHD, and potentially for other T-cell-mediated pathologies.