Bortezomib modulates regulatory T cell subpopulations in the process of acute graft-versus-host disease.

Background: Acute graft-versus-host disease (aGVHD) combines the wide application of allogeneic bone marrow transplantation (allo-BMT). Recent studies indicate that it is possible to reduce the incidence and severity of aGVHD by using bortezomib. In this study, we explored the changes of T cell subsets after allo-BMT with bortezomib, in order to elucidate the mechanism by which bortezomib attenuates aGVHD. Methods: Following a single dose of lethal irradiation (TBI, 0.7 Gy/minutes, 8.0 Gy), BALB/c mice were injected with 2x10(7) C57BL/6 nucleated BM cells plus 1x10(7) splenocytes with or without bortezomib at 1.0 mg/kg. The ratio of CD4(+)CD25(+) Foxp(3+) regulatory T cells (Treg) was examined by flow cytometry, and the cytokine levels of IL-2 (Th1) and IL-4 (Th2) were detected by ELISA. Bivariate correlation analysis was carried out to evaluate changes of the Th1 and Th2 cytoldnes related to the changes of Treg. Results: Bortezomib remarkably reduced aGVHD severity and prolonged the survival time. Along with bortezomib injection, the ratio of Treg was significantly increased and IL-2 level was decreased but IL-4 level was increased. Bivariate correlation analysis results evaluated the correlation between the increment of Treg and changes of Th1 and Th2 cytokines. Conclusions: Bortezomib may exert its effect by triggering the generation of Treg which might regulate the imbalance of Th1/Th2 during aGVHD.