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Publication : Intravital imaging of donor allogeneic effector and regulatory T cells with host dendritic cells during GVHD.

First Author  Lin KL Year  2014
Journal  Blood Volume  123
Issue  10 Pages  1604-14
PubMed ID  24415540 Mgi Jnum  J:209503
Mgi Id  MGI:5568012 Doi  10.1182/blood-2013-09-526020
Citation  Lin KL, et al. (2014) Intravital imaging of donor allogeneic effector and regulatory T cells with host dendritic cells during GVHD. Blood 123(10):1604-14
abstractText  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.
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