Graft-infiltrating host dendritic cells play a key role in organ transplant rejection

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 () and Adrian E. Morelli ()
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Quan Zhuang: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Quan Liu: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Sherrie J. Divito: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Qiang Zeng: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Karim M. Yatim: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Andrew D. Hughes: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Darling M. Rojas-Canales: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
A. Nakao: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
William J. Shufesky: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Amanda L. Williams: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Rishab Humar: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Rosemary A. Hoffman: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Warren D. Shlomchik: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Martin H. Oberbarnscheidt: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Fadi G. Lakkis: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine
Adrian E. Morelli: Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract Successful engraftment of organ transplants has traditionally relied on preventing the activation of recipient (host) T cells. Once T-cell activation has occurred, however, stalling the rejection process becomes increasingly difficult, leading to graft failure. Here we demonstrate that graft-infiltrating, recipient (host) dendritic cells (DCs) play a key role in driving the rejection of transplanted organs by activated (effector) T cells. We show that donor DCs that accompany heart or kidney grafts are rapidly replaced by recipient DCs. The DCs originate from non-classical monocytes and form stable, cognate interactions with effector T cells in the graft. Eliminating recipient DCs reduces the proliferation and survival of graft-infiltrating T cells and abrogates ongoing rejection or rejection mediated by transferred effector T cells. Therefore, host DCs that infiltrate transplanted organs sustain the alloimmune response after T-cell activation has already occurred. Targeting these cells provides a means for preventing or treating rejection.

Date: 2016
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DOI: 10.1038/ncomms12623

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