Abstract
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Bortezomib Modulates Regulatory T Cell Subpopulations in the Process of Acute Graft-Versus-Host Disease
by Jianyu Weng, Peilong Lai, Meikun Lv, Shaoze Lin, Wei Ling, Suxia Geng, Chenwei Luo, Xiaoli Liu, Xin Du
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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 2×107 C57BL/6 nucleated BM cells plus 1×107 splenocytes with or without bortezomib at 1.0 mg/kg. The ratio of CD4+CD25+ Foxp3+ 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 cytokines 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.
DOI: 10.7754/Clin.Lab.2012.120215
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