Activation of natural killer cells and macrophages by porcine endothelial cells augments specific T-cell xenoresponse

Xiao Chun Xu, Jeremy Goodman, Hitomi Sasaki, Jeffrey Lowell, T. Mohanakumar

研究成果: Article査読

28 被引用数 (Scopus)

抄録

The rejection of xenografts is characterized by infiltration of monocytes and natural killer (NK) cells into the graft, suggesting an important role for the innate immune system in xenorecognition. In this study, purified human NK or T cells were cocultured with porcine endothelial cells, and cytokines were analyzed by ELISA and intracellular FACS. We demonstrated a vigorous human anti-porcine xenoresponse that was associated with a strong T-cell proliferation against porcine endothelial cells. Limiting dilution cloning and T-cell receptor (TCR) Vp gene usage revealed a low number of xenoreactive T-cell precursors. We demonstrated that xenogeneic porcine but not allogeneic human endothelial cells induced the early production of interferon (IFN)-γ by human NK cells but not by CD3+ T cells. Porcine xenoantigen-induced IFN-γ production was only partially dependent on IL-12. Blocking IL-12 with neutralizing antibodies or by depletion of human macrophages partially decreased IFN-γ production by CD56+ NK cells. Three-color flow cytometry revealed that IL-12 was produced through a species-specific activation of human macrophages by porcine endothelial cells. Our results indicate that the direct activation of NK cells and macrophages by porcine endothelial cells provides a unique pathway of xenorecognition that augments downstream specific T-cell immunity and represents a powerful effector mechanism in xenograft rejection.

本文言語English
ページ(範囲)314-322
ページ数9
ジャーナルAmerican Journal of Transplantation
2
4
DOI
出版ステータスPublished - 04-2002
外部発表はい

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 移植
  • 薬理学(医学)

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