Granulocyte colony-stimulating factor-induced immature myeloid cells inhibit acute graft-versus-host disease lethality through an indoleamine dioxygenase-independent mechanism.
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-gamma (IFN-gamma). This level was significantly higher in IFN-gamma-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.
Joo
Young-Don
YD
Department of Hemato/Oncology, Busan Paik Hospital, College of Medicine, Inje University, Busan, Korea.
Lee
Sun-Mi
SM
Lee
Soo-Woong
SW
Lee
Won-Sik
WS
Lee
Sang-Min
SM
Park
Ji-Kyoung
JK
Choi
Il-Whan
IW
Park
Sae-Gwang
SG
Choi
Inhak
I
Seo
Su-Kil
SK
D000208:Acute Disease; D000818:Animals; D017690:Cell Transplantation; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007165:Immunosuppression Therapy; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016179:Granulocyte Colony-Stimulating Factor; D007371:Interferon-gamma