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, Adrian E. Morelli

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42 Citations (Scopus)

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.

Original languageEnglish
Article number12623
Number of pages12
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 24 Aug 2016
Externally publishedYes

Keywords

  • Graft-Infiltrating
  • Dendritic Cells
  • Organ Transplant Rejection

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    Zhuang, Q., Liu, Q., Divito, S. J., Zeng, Q., Yatim, K. M., Hughes, A. D., Rojas-Canales, D. M., Nakao, A., Shufesky, W. J., Williams, A. L., Humar, R., Hoffman, R. A., Shlomchik, W. D., Oberbarnscheidt, M. H., Lakkis, F. G., & Morelli, A. E. (2016). Graft-infiltrating host dendritic cells play a key role in organ transplant rejection. Nature Communications, 7, [12623]. https://doi.org/10.1038/ncomms12623