title: Immunosuppressive CD14+HLA-DRlow/neg IDO+ myeloid cells in patients following allogeneic hematopoietic stem cell transplantation.
abstract: Myeloid-derived suppressor cells (MDSCs) have emerged as a heterogeneic immunoregulatory population that can expand in response to inflammatory signals. Predominantly studied in cancer, MDSCs suppress T cells utilizing various mechanisms. In allogeneic hematopoietic stem cell transplantation (allo-HSCT) therapy-related toxicity and alloreactivity increase inflammatory cytokines that might favor an MDSC accumulation. To address this question, circulating CD14(+)HLA-DR(low/neg) cells were studied retrospectively in 51 allo-HSCT patients. These cells represent one of the few well-described human MDSC subsets under physiological and pathological conditions. The frequency of CD14(+)HLA-DR(low/neg) cells was significantly increased after allo-HSCT, especially in patients with acute graft-versus-host disease. Compared to healthy donor cells they were pSTAT1(low) (phosphorylated signal transducer and activator of transcription) and indoleamine 2,3-dioxygenase (IDO)(high). Serum levels of granulocyte colony-stimulating factor and interleukin-6, which both have been linked to MDSC induction, correlated positively with the frequency of CD14(+)HLA-DR(low/neg) cells. In vitro dysfunction of patient T cells, such as reduced proliferative capacity or CD3ζ-chain expression, was rescued by blocking the IDO activity of CD14(+)HLA-DR(low/neg) cells. Overall, we identified a T-cell-suppressive monocytic population that expands after allo-HSCT. The mechanisms responsible for such accumulation remain to be elucidated. It will be of great interest to prospectively investigate the influence of these cells on the graft-versus-tumor and -host reaction.
authors: Division of Clinical Immunology, Karolinska University Hospital Huddinge, Stockholm, Sweden. dimitrios.mougiakakos@uk-erlangen.de
authors: D
authors: D
authors: Mougiakakos
authors: R
authors: R
authors: Jitschin
authors: L
authors: L
authors: von Bahr
authors: I
authors: I
authors: Poschke
authors: R
authors: R
authors: Gary
authors: B
authors: B
authors: Sundberg
authors: A
authors: A
authors: Gerbitz
authors: P
authors: P
authors: Ljungman
authors: K
authors: K
authors: Le Blanc
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology* / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism*; D019337:Hematologic Neoplasms / Q000150:complications* / Q000276:immunology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007165:Immunosuppression Therapy; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D010766:Phosphorylation; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014182:Transplantation, Autologous; D055815:Young Adult
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D016179:Granulocyte Colony-Stimulating Factor