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

M Koyama, D Hashimoto, K Aoyama… - Blood, The Journal …, 2009 - ashpublications.org
M Koyama, D Hashimoto, K Aoyama, K Matsuoka, K Karube, H Niiro, M Harada, M Tanimoto…
Blood, The Journal of the American Society of Hematology, 2009ashpublications.org
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 …
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 outcomes 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 in the absence of other DC subsets and to provide important insight into developing strategies for tolerance induction in transplantation.
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