Abstract:
:Graft-versus-host disease (GVHD) is a systemic inflammatory response due to the recognition of major histocompatibility complex disparity between donor and recipient after hematopoietic stem cell transplantation (HSCT). T-cell activation is critical to the induction of GVHD, and data from our group and others have shown that regulatory T cells (Tregs) prevent GVHD when given at the time of HSCT. Using multiphoton laser scanning microscopy, we examined the single cell dynamics of donor T cells and dendritic cells (DCs) with or without Tregs postallogeneic transplantation. We found that donor conventional T cells (Tcons) spent very little time screening host DCs. Tcons formed stable contacts with DCs very early after transplantation and only increased velocity in the lymph node at 20 hours after transplant. We also observed that Tregs reduced the interaction time between Tcons and DCs, which was dependent on the generation of interleukin 10 by Tregs. Imaging using inducible Tregs showed similar disruption of Tcon-DC contact. Additionally, we found that donor Tregs induce host DC death and down-regulate surface proteins required for donor T-cell activation. These data indicate that Tregs use multiple mechanisms that affect host DC numbers and function to mitigate acute GVHD.
journal_name
Bloodjournal_title
Bloodauthors
Lin KL,Fulton LM,Berginski M,West ML,Taylor NA,Moran TP,Coghill JM,Blazar BR,Bear JE,Serody JSdoi
10.1182/blood-2013-09-526020subject
Has Abstractpub_date
2014-03-06 00:00:00pages
1604-14issue
10eissn
0006-4971issn
1528-0020pii
blood-2013-09-526020journal_volume
123pub_type
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