Adrian E Morelli1. 1. T.E. Starzl Transplantation Institute and Departments of Surgery and Immunology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Abstract
PURPOSE OF REVIEW: Advances in surgery, patient management, and pharmacologic immunosuppression have reduced the incidence of acute allograft rejection. However, generation of therapies to promote donor-specific immunosuppression with minimal side-effects has proved to be a difficult task. To some extent, this is because of our limited knowledge on how Ag-presenting cells (APCs) like dendritic cells initiate and maintain the antidonor response in vivo. Herein, we link the classic concepts on the role of donor's dendritic cells as passenger leukocytes with the state-of-the-art findings in the field. RECENT FINDINGS: Numerous studies are starting to unveil the plethora of mediators and interactions with leukocytes that trigger maturation of donor's dendritic cells in the grafts. The concept that donor's dendritic cells migrate from the grafts to secondary lymphoid organs to prime T cells has been challenged in murine models of lung or intestine transplantation, in which T cells can also be primed in the allograft. Increasing evidence suggests that recipient's dendritic cells present donor's intact major histocompatibility complex (MHC) molecules in lymphoid organs and that they infiltrate the grafts. SUMMARY: A more complete understanding of the role of dendritic cells in allosensitization will help to develop better dendritic cell-based therapies to achieve the final goal of promoting donor-specific immunosuppression.
PURPOSE OF REVIEW: Advances in surgery, patient management, and pharmacologic immunosuppression have reduced the incidence of acute allograft rejection. However, generation of therapies to promote donor-specific immunosuppression with minimal side-effects has proved to be a difficult task. To some extent, this is because of our limited knowledge on how Ag-presenting cells (APCs) like dendritic cells initiate and maintain the antidonor response in vivo. Herein, we link the classic concepts on the role of donor's dendritic cells as passenger leukocytes with the state-of-the-art findings in the field. RECENT FINDINGS: Numerous studies are starting to unveil the plethora of mediators and interactions with leukocytes that trigger maturation of donor's dendritic cells in the grafts. The concept that donor's dendritic cells migrate from the grafts to secondary lymphoid organs to prime T cells has been challenged in murine models of lung or intestine transplantation, in which T cells can also be primed in the allograft. Increasing evidence suggests that recipient's dendritic cells present donor's intact major histocompatibility complex (MHC) molecules in lymphoid organs and that they infiltrate the grafts. SUMMARY: A more complete understanding of the role of dendritic cells in allosensitization will help to develop better dendritic cell-based therapies to achieve the final goal of promoting donor-specific immunosuppression.
Authors: Quan Zhuang; Quan Liu; Sherrie J Divito; Qiang Zeng; Karim M Yatim; Andrew D Hughes; Darling M Rojas-Canales; A Nakao; William J Shufesky; Amanda L Williams; Rishab Humar; Rosemary A Hoffman; Warren D Shlomchik; Martin H Oberbarnscheidt; Fadi G Lakkis; Adrian E Morelli Journal: Nat Commun Date: 2016-08-24 Impact factor: 14.919