Utility of novel T-cell-specific extracellular vesicles in monitoring and evaluation of acute GVHD.

We have recently reported a new method for detecting T-cell-derived extracellular vesicles (EVs), CD3CD4EVs,CD3CD8EVs, and CD3HLA-DREVs. In our previous study, CD3HLA-DREVs were released profusely by CD8T cells, only moderately by T helper1 (Th1) CD4T cells, and very little from Th2 CD4T cells in vitro. EVs were measured sequentially in patients undergoing hematopoietic stem cell transplantation (HSCT), and their relationship to GVHD was investigated in comparison with other conventional biomarkers. We analyzed peripheral blood samples from 20 patients (13 children and 7 adults) who underwent HSCT at Tokyo Medical and Dental University Hospital. CD3CD4EV and CD3CD8EV levels specifically correlated with the CD4 and CD8T lymphocyte counts, respectively. CD3CD8EVs and CD3HLA-DREVs increased in GVHD and reflected the persistence of GVHD more specifically than soluble IL-2 receptor (sIL-2R). In engraftment syndrome, sIL-2R was markedly elevated, but CD3HLA-DREVs were not. Furthermore, ferritin and sIL-2R markedly increased in hemophagocytic syndrome (HPS) that developed before engraftment; however, the change in CD3HLA-DREVs was marginal. CD3CD4, CD3CD8, and CD3HLA-DREVs efficiently reflect the cell-mediated immune response, and CD3CD8EVs and CD3HLA-DREVs are more useful than other conventional biomarkers, such as sIL-2R, for monitoring and evaluation of acute GVHD.