TY - JOUR
T1 - Graft-infiltrating host dendritic cells play a key role in organ transplant rejection
AU - Zhuang, Quan
AU - Liu, Quan
AU - Divito, Sherrie J.
AU - Zeng, Qiang
AU - Yatim, Karim M.
AU - Hughes, Andrew D.
AU - Rojas-Canales, Darling M.
AU - Nakao, A.
AU - Shufesky, William J.
AU - Williams, Amanda L.
AU - Humar, Rishab
AU - Hoffman, Rosemary A.
AU - Shlomchik, Warren D.
AU - Oberbarnscheidt, Martin H.
AU - Lakkis, Fadi G.
AU - Morelli, Adrian E.
PY - 2016/8/24
Y1 - 2016/8/24
N2 - 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.
AB - 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.
KW - Graft-Infiltrating
KW - Dendritic Cells
KW - Organ Transplant Rejection
UR - http://www.scopus.com/inward/record.url?scp=84984713101&partnerID=8YFLogxK
U2 - 10.1038/ncomms12623
DO - 10.1038/ncomms12623
M3 - Article
C2 - 27554168
AN - SCOPUS:84984713101
SN - 2041-1723
VL - 7
JO - Nature Communications
JF - Nature Communications
M1 - 12623
ER -