Granulocyte colony‐stimulating factor‐induced immature myeloid cells inhibit acute graft‐versus‐host disease lethality through an indoleamine dioxygenase‐independent mechanism
Open Access
- 4 August 2009
- journal article
- Published by Wiley in Immunology
- Vol. 128 (1pt2), e632-e640
- https://doi.org/10.1111/j.1365-2567.2009.03048.x
Abstract
Granulocyte colony-stimulating factor (G-CSF)-mobilized donor graft tissue used for peripheral blood stem cell transplantation contains a large number of immature myeloid cells that suppress alloreactive donor T cells, resulting in an inhibition of acute graft-versus-host disease (GVHD). However, the molecular mechanism underlying the suppressive function of immature myeloid cells is not fully understood. Here, we investigated whether indoleamine 2,3-dioxygenase (IDO) is related to the suppressive mechanism of G-CSF-induced immature myeloid cells (gMCs). We found that Gr-1+ CD11b+ cells were highly induced in G-CSF-injected donor graft tissue, which is a phenotype of immature myeloid cells, resulting in an inhibition of acute GVHD lethality by suppressing alloreactive donor T-cell expansion. IDO was not detected in primary isolated gMCs; however, this enzyme was markedly induced after treatment with interferon-γ (IFN-γ). This level was significantly higher in IFN-γ-treated gMCs than in bone marrow myeloid cells, which promote alloreactive T-cell responses. We next investigated the functional role of IDO in gMC-mediated inhibition of acute GVHD lethality. We found no changes in gMC-mediated survival or alloreactive donor T-cell suppression when IDO activity was blocked using 1-methyl tryptophan. In addition, there was no difference in gMC-mediated survival rates between recipients transferred with either wild-type gMCs or IDO−/− gMCs. Taken together, our data suggest that gMC-mediated inhibition of lethal acute GVHD is through an IDO-independent mechanism.Keywords
This publication has 45 references indexed in Scilit:
- Histone deacetylase inhibition modulates indoleamine 2,3-dioxygenase–dependent DC functions and regulates experimental graft-versus-host disease in miceJCI Insight, 2008
- Thymosin α1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and toleranceBlood, 2006
- Stem cell mobilization with G-CSF analogs: a rational approach to separate GVHD and GVL?Blood, 2006
- G-CSF-treated granulocytes inhibit acute graft-versus-host diseaseBlood, 2006
- Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase–mediated tryptophan degradationBlood, 2004
- Chronic graft-versus-host disease after allogeneic blood stem cell transplantation: long-term results of a randomized studyBlood, 2002
- T cell infiltration and chemokine expression: relevance to the disease localization in murine graft-versus-host diseaseBone Marrow Transplantation, 2002
- Donor-derived interferon γ separates graft-versus-leukemia effects and graft-versus-host disease induced by donor CD8 T cellsBlood, 2002
- Influence of recombinant human granulocyte colony-stimulating factor (filgrastim) on hematopoietic recovery and outcome following allogeneic bone marrow transplantation (BMT) from volunteer unrelated donorsBone Marrow Transplantation, 1999
- Allogeneic peripheral blood stem cell transplantation for haematological malignancies – an analysis of kinetics of engraftment and GVHD riskBone Marrow Transplantation, 1997