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

Research output: Contribution to journalArticle

72 Citations (Scopus)

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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T-cells
Graft vs Host Disease
Antigen-Presenting Cells
Grafts
Dendritic Cells
T-Lymphocytes
Antigens
Isoantigens
Toll-Like Receptors
Hematopoietic Stem Cell Transplantation
Stem cells
Major Histocompatibility Complex
Cell Communication
Immunity
Transplantation
Irradiation

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Plasmacytoid dendritic cells prime alloreactive T cells to mediate graft-versus-host disease as antigen-presenting cells. / Koyama, Motoko; Hashimoto, Daigo; Aoyama, Kazutoshi; Matsuoka, Ken-ichi; Karube, Kennosuke; Niiro, Hiroaki; Harada, Mine; Tanimoto, Mitsune; Akashi, Koichi; Teshima, Takanori.

In: Blood, Vol. 113, No. 9, 26.02.2009, p. 2088-2095.

Research output: Contribution to journalArticle

Koyama, M, Hashimoto, D, Aoyama, K, Matsuoka, K, 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, vol. 113, no. 9, pp. 2088-2095. https://doi.org/10.1182/blood-2008-07-168609
Koyama, Motoko ; Hashimoto, Daigo ; Aoyama, Kazutoshi ; Matsuoka, Ken-ichi ; Karube, Kennosuke ; Niiro, Hiroaki ; Harada, Mine ; Tanimoto, Mitsune ; Akashi, Koichi ; Teshima, Takanori. / Plasmacytoid dendritic cells prime alloreactive T cells to mediate graft-versus-host disease as antigen-presenting cells. In: Blood. 2009 ; Vol. 113, No. 9. pp. 2088-2095.
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