3Transplant Surgery, Tokyo Medical University, Hachioji, Tokyo, Japan.
Modulating T Cell Migration in the Postischemic Liver: Hepatic Stellate Cells as New Therapeutic Target?
Background: It is clear that T cells play a central role in the process of allograft rejection. However, donor dendritic cells (dDC) are the most potent antigen-presenting cells and have proven to be major regulators in determining the fate of the alloimmune response. By monitoring the complex behavior of cells, it will possible to answer many of outstanding questions in the field.
We have now adapted the use of intravital microscopy (IVM) to track EYFP DC motility, morphology, and cell density in real-time.
Since dDC located at graft are exposed to host cells right after reperfusion, our recent findings could provide us the following possibilities; 1) dDC have already been activated during ischemic time to prepare for start cross-talking with host cells right after reperfusion, and 2) dDC are the most potent antigen presenting cells, which suggest dDC might play an emerging role as a bridge between innate immunity and alloimmunity in cardiac transplant model.
To our knowledge, this is the first observation that T cells can be primed by interactions with dDC outside of secondary lymphoid tissues following transplantation within an hour. If this is the case, dDC could be the most potent therapeutic target in cardiac transplant model.
Ueno T, Yeung M, McGrath M, Iwamoto H, Nakamura Y, Konnno O, Kihara Y, Yokoyama T, Ono S, Ikeda T, Kawachi S, Ibrahim B, Chandraker A. Donor Dendritic Cells – Potential New Therapeutic Target in Transplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-dendritic-cells-potential-new-therapeutic-target-in-transplantation/. Accessed April 18, 2019.