Graft-versus-Host Disease Prevents the Maturation of Plasmacytoid Dendritic Cells

Tatjana Banovic, Kate A. Markey, Rachel D. Kuns, Stuart D. Olver, Neil C. Raffelt, Alistair L. Don, Mariapia A. Degli-Esposti, Christian R. Engwerda, Kelli P. A. MacDonald and Geoffrey R. Hill (2009) Graft-versus-Host Disease Prevents the Maturation of Plasmacytoid Dendritic Cells. Journal of Immunology, 182 2: 912-920.


Author Tatjana Banovic
Kate A. Markey
Rachel D. Kuns
Stuart D. Olver
Neil C. Raffelt
Alistair L. Don
Mariapia A. Degli-Esposti
Christian R. Engwerda
Kelli P. A. MacDonald
Geoffrey R. Hill
Title Graft-versus-Host Disease Prevents the Maturation of Plasmacytoid Dendritic Cells
Formatted title
Graft-versus-Host Disease Prevents the Maturation of Plasmacytoid Dendritic Cells
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2009-01-15
Year available 2009
Sub-type Article (original research)
Volume 182
Issue 2
Start page 912
End page 920
Total pages 9
Editor Jeremy M Boss
Michele M Hogan
Place of publication United States
Publisher United States
Collection year 2010
Language eng
Subject C1
9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
1103 Clinical Sciences
Abstract The role of Ag presenting cell subsets in graft-versus-host disease (GVHD) remains unclear. We have thus examined the ability of plasmacytoid dendritic cells (pDC) to modulate transplant outcome. Surprisingly, host pDC were exquisitely sensitive to total body irradiation and were depleted before transplantation, thus allowing us to focus on donor pDC. The depletion of all pDC from bone marrow grafts resulted in an acceleration of GVHD mortality while the depletion of mature pDC from G-CSF mobilized splenic grafts had no effect. Thus, donor bone marrow pDC, but not mature pDC contained within stem cell grafts attenuate acute GVHD. In the presence of GVHD, donor pDC completely failed to reconstitute although a CD11clow120G8+ precursor DC reconstituted in an exaggerated and transient manner. These cells expressed Flt-3, the macrophage colony stimulating factor receptor and, consistent with a common dendritic cell (DC) precursor, were capable of differentiation into pDC and conventional DC in vivo in the absence of GVHD. These precursors were MHC class II+ and CD80/86+ but lacked CD40, were actively presenting host Ag and inhibited GVHD and T cell proliferation in a contact-dependent fashion. These data demonstrate that GVHD prevents the maturation of pDC and instead promotes the generation of a suppressive precursor DC, further contributing to the state of immune paralysis after transplantation.
Formatted abstract
The role of Ag presenting cell subsets in graft-versus-host disease (GVHD) remains unclear. We have thus examined the ability of plasmacytoid dendritic cells (pDC) to modulate transplant outcome. Surprisingly, host pDC were exquisitely sensitive to total body irradiation and were depleted before transplantation, thus allowing us to focus on donor pDC. The depletion of all pDC from bone marrow grafts resulted in an acceleration of GVHD mortality while the depletion of mature pDC from G-CSF mobilized splenic grafts had no effect. Thus, donor bone marrow pDC, but not mature pDC contained within stem cell grafts attenuate acute GVHD. In the presence of GVHD, donor pDC completely failed to reconstitute although a CD11clow120G8+ precursor DC reconstituted in an exaggerated and transient manner. These cells expressed Flt-3, the macrophage colony stimulating factor receptor and, consistent with a common dendritic cell (DC) precursor, were capable of differentiation into pDC and conventional DC in vivo in the absence of GVHD. These precursors were MHC class II+ and CD80/86+ but lacked CD40, were actively presenting host Ag and inhibited GVHD and T cell proliferation in a contact-dependent fashion. These data demonstrate that GVHD prevents the maturation of pDC and instead promotes the generation of a suppressive precursor DC, further contributing to the state of immune paralysis after transplantation.
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Tue, 30 Mar 2010, 14:10:03 EST by Amanda Jones on behalf of Medicine - Royal Brisbane and Women's Hospital