Abstract 4709

Objective:

Acute graft-versus-host disease (aGVHD) confines the wider application of allogeneic bone marrow transplantation (allo-BMT), but recently studies indicate that it is possible to reduce the incidence and severity of aGVHD while preserving the GVT by using bortezomib. In current study, we explored the changes of T cell subsets after allo-BMT administrated with bortezomib immediately, in order to establish the mechanism about bortezomib attenuation aGVHD.

Materials and Methods:

BALB/c mouse were injected of 0.5 mL PBS containing C57BL/6 2×107 nucleated BM cells plus 1×107 splenocytes followed a single dose of lethal total body irradiation (TBI, 0.7 Gy/min, 8.0 Gy) with or without bortezomib at 1.0 mg/kg. The level of CD4+ CD25+ Foxp3+ regulator T cells is quantified by flow cytometry, and the cytokine level of IL-2 and IL-4 is quantified by ELISA.

Results:

Bortezomib remarkably reduce aGVHD severity and prolonged the surviving time. Along with bortezomib injection, the level of CD4+ CD25+ Foxp3+ regulator T cell is significantly increased, the cytokine level of IL-2 is decreased but IL-4 is increased.

Conclusion:

Bortezomib inhibit aGVHD through shifting the combination of T cell subpopulations with up regulation CD4+CD25+ Foxp3+ regulator T cells lead to reset Th1/Th2 cytokine balance.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
bortezomib, graft-versus-host disease, acute, t-lymphocytes, bone marrow transplantation, allogeneic, cytokine, aldesleukin, interleukin-4, flow cytometry, painful bladder syndrome, single-dose regimen

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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