Plasmacytoid dendritic cells prime alloreactive T cells to mediate graft-versus-host disease as antigen-presenting cells

Motoko Koyama, Daigo Hashimoto, Kazutoshi Aoyama, Ken Ichi Matsuoka, Kennosuke Karube, Hiroaki Niiro, Mine Harada, Mitsune Tanimoto, Koichi Akashi, Takanori Teshima

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Abstract

Dendritic cells (DCs) can be classified into 2 distinct subsets: conventional DCs (cDCs) and plasmacytoid DCs (pDCs). cDCs can prime antigen-specific T-cell immunity, whereas in vivo function of pDCs as antigen-presenting cells remains controversial. We evaluated the contribution of pDCs to allogeneic T-cell responses in vivo in mouse models of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation by an add-back study of MHC-expressing pDCs into major histocompatibility complex-deficient mice that were resistant to GVHD. Alloantigen expression on pDCs alone was sufficient to prime alloreactive T cells and cause GVHD.An inflammatory environment created by host irradiation has the decisive role in maturing pDCs for T-cell priming but this process does not require Toll-like receptor signaling. Thus, functional out-comes of pDC-T-cell interactions depend on the immunologic context of encounter. To our knowledge, these results are the first to directly demonstrate an in vivo pathogenic role of pDCs as antigen-presenting cells in an antigen-specific T cell-mediated disease inthe absence of other DC subsets and to provide important insight into developing strategies for tolerance induction in transplantation.

Original languageEnglish
Pages (from-to)2088-2095
Number of pages8
JournalBlood
Volume113
Issue number9
DOIs
Publication statusPublished - Feb 26 2009

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Koyama, M., Hashimoto, D., Aoyama, K., Matsuoka, K. I., Karube, K., Niiro, H., Harada, M., Tanimoto, M., Akashi, K., & Teshima, T. (2009). Plasmacytoid dendritic cells prime alloreactive T cells to mediate graft-versus-host disease as antigen-presenting cells. Blood, 113(9), 2088-2095. https://doi.org/10.1182/blood-2008-07-168609