title: IL-10 induces the development of immunosuppressive CD14(+)HLA-DR(low/-) monocytes in B-cell non-Hodgkin lymphoma.
abstract: The biological role of monocytes and macrophages in B-cell non-Hodgkin lymphoma (NHL) is not fully understood. We have previously reported that monocytes from patients with B-cell NHL have an immunosuppressive CD14(+)HLA-DR(low/-) phenotype that correlates with a poor prognosis. However, the underlying mechanism by which CD14(+)HLA-DR(low/-) monocytes develop in lymphoma is unknown. In the present study, we found that interleukin (IL)-10, which is increased in the serum of patients with B-cell NHL, induced the development of the CD4(+)HLA-DR(low/-) population. Using peripheral blood samples from patients with B-cell NHL, we found that absolute numbers of CD14(+) monocytic cells with an HLA-DR(low/-) phenotype were higher than healthy controls and correlated with a higher International Prognostic Index score. IL-10 serum levels were elevated in lymphoma patients compared with controls and were associated with increased peripheral monocyte counts. Treatment of monocytes with IL-10 in vitro significantly decreased HLA-DR expression and resulted in the expansion of CD14(+)HLA-DR(low/-) population. We found that lymphoma B cells produce IL-10 and supernatants from cultured lymphoma cells increased the CD14(+)HLA-DR(low/-) population. Furthermore, we found that IL-10-induced CD14(+)HLA-DR(low/-) monocytes inhibited the activation and proliferation of T cells. Taken together, these results suggest that elevated IL-10 serum levels contribute to increased numbers of immunosuppressive CD14(+)HLA-DR(low/-) monocytes in B-cell NHL.
authors.affiliation: 1] Department of Hematology, Tongji Hospital, Tongji University, Shanghai, China [2] Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: B
authors.initials: B
authors.lastname: Xiu
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Grote
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Ziesmer
authors.affiliation: Division of Transfusion Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Gustafson
authors.affiliation: Division of Transfusion Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Maas
authors.affiliation: Division of Transfusion Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Division of Transfusion Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Dietz
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: L F
authors.initials: LF
authors.lastname: Porrata
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Novak
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji University, Shanghai, China.
authors.forename: A-B
authors.initials: AB
authors.lastname: Liang
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Z-Z
authors.initials: ZZ
authors.lastname: Yang
authors.affiliation: Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Ansell
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008213:Lymphocyte Activation; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000276:immunology*; D009000:Monocytes / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D006684:HLA-DR Antigens; C508609:IL10 protein, human; D018950:Lipopolysaccharide Receptors; D016753:Interleukin-10