Immunosuppressive CD14+HLA-DRlow/neg IDO+ myeloid cells in patients following allogeneic hematopoietic stem cell transplantation.

Publisher: Nature Publishing Group, Specialist Journals Country of Publication: England NLM ID: 8704895 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5551 (Electronic) Linking ISSN: 08876924 NLM ISO Abbreviation: Leukemia Subsets: MEDLINE

Publication: 2000- : London : Nature Publishing Group, Specialist Journals
Original Publication: [Baltimore, Md.] : Williams & Wilkins, [c1987-

Immunosuppression Therapy*; Graft vs Host Disease/*etiology ; HLA-DR Antigens/*metabolism ; Hematologic Neoplasms/*complications ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Indoleamine-Pyrrole 2,3,-Dioxygenase/*metabolism ; Lipopolysaccharide Receptors/*metabolism ; Myeloid Cells/*immunology; Adolescent ; Adult ; Aged ; Blotting, Western ; Cell Proliferation ; Cytokines/genetics ; Cytokines/metabolism ; Female ; Flow Cytometry ; Follow-Up Studies ; Graft vs Host Disease/metabolism ; Granulocyte Colony-Stimulating Factor/genetics ; Granulocyte Colony-Stimulating Factor/metabolism ; Hematologic Neoplasms/immunology ; Hematologic Neoplasms/therapy ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics ; Male ; Middle Aged ; Monocytes/immunology ; Monocytes/metabolism ; Monocytes/pathology ; Myeloid Cells/metabolism ; Myeloid Cells/pathology ; Oxidative Stress ; Phosphorylation ; Prognosis ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; STAT1 Transcription Factor/genetics ; STAT1 Transcription Factor/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes/pathology ; Transplantation, Autologous ; Young Adult

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.

0 (Cytokines)
0 (HLA-DR Antigens)
0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
0 (Lipopolysaccharide Receptors)
0 (RNA, Messenger)
0 (STAT1 Transcription Factor)
0 (STAT1 protein, human)
143011-72-7 (Granulocyte Colony-Stimulating Factor)

Date Created: 20120726 Date Completed: 20130404 Latest Revision: 20211203

20250114

10.1038/leu.2012.215

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