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.
N1 - Funding Information:
This work was supported by grants from the US National Institutes of Health (R01 AI049466 and R01 AI099465 to F.G.L., and R01 HL130191 to A.E.M.); American Society of Nephrology (Merrill Grant in Transplantation to MHO and Donald E. Wesson Research Fellowship to KMY); American Heart Association (14GRNT19810000 to A.E.M.); the National Natural Science Foundation of China NSFC81401318 (to Q.L.) and the Frank and Athena Sarris Chair in Transplantation Biology to F.G.L.
Publisher Copyright:
© The Author(s) 2016.
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.
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U2 - 10.1038/ncomms12623
DO - 10.1038/ncomms12623
M3 - Article
C2 - 27554168
AN - SCOPUS:84984713101
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 12623
ER -