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IL-10 induces the development of immunosuppressive CD14(+)HLA-DR(low/-) monocytes in B-cell non-Hodgkin lymphoma.

Xiu B, Lin Y, Grote DM, Ziesmer SC, Gustafson MP, Maas ML, Zhang Z, Dietz AB, Porrata LF, Novak AJ, Liang AB, Yang ZZ, Ansell SM - Blood Cancer J (2015)

Bottom Line: 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.We found that lymphoma B cells produce IL-10 and supernatants from cultured lymphoma cells increased the CD14(+)HLA-DR(low/-) population.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Hematology, Tongji Hospital, Tongji University, Shanghai, China [2] Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Absolute numbers of monocytes are increased in B-cell NHL. (a and b) A graph showing absolute monocyte counts in blood from NHL patients and healthy donors (a) or patients with different histologies (b) measured by flow cytometry. DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma. One milliliter freshly drawn whole blood was stained with a panel of Abs and analyzed by flow cytometry. Absolute monocyte counts were calculated as the numbers of CD14+ cells per microliter of blood (NHL: n=22, Ctrl: n=26). (c) Representative plots showing coexpression of CD14 and CD16 in blood from a healthy donor. Classical monocytes: CD14++CD16−; intermediate monocytes: CD14++CD16+; non-classical monocytes: CD14+CD16++. (d) Graphs showing the absolute counts (upper panel) or percentages (lower panel) of classical, intermediate and non-classical monocytes (Mo) in blood from NHL patients and healthy donors measured by flow cytometry.
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fig1: Absolute numbers of monocytes are increased in B-cell NHL. (a and b) A graph showing absolute monocyte counts in blood from NHL patients and healthy donors (a) or patients with different histologies (b) measured by flow cytometry. DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma. One milliliter freshly drawn whole blood was stained with a panel of Abs and analyzed by flow cytometry. Absolute monocyte counts were calculated as the numbers of CD14+ cells per microliter of blood (NHL: n=22, Ctrl: n=26). (c) Representative plots showing coexpression of CD14 and CD16 in blood from a healthy donor. Classical monocytes: CD14++CD16−; intermediate monocytes: CD14++CD16+; non-classical monocytes: CD14+CD16++. (d) Graphs showing the absolute counts (upper panel) or percentages (lower panel) of classical, intermediate and non-classical monocytes (Mo) in blood from NHL patients and healthy donors measured by flow cytometry.

Mentions: To determine the role of immune cells in NHL, we first measured the numbers of mononuclear phagocytes (monocytes, myeloid-derived suppressor cells, macrophages, dendritic cells), T cells and natural killer T cells by flow cytometry in the peripheral blood from 22 newly diagnosed NHL patients, including diffuse large B-cell lymphoma (n=6), follicular lymphoma (n=7), mantle cell lymphoma (n=4) and marginal zone lymphoma (n=5), and healthy donors matched for age and gender (n=26). As shown in Figure 1a, the absolute numbers of CD14+ monocytes were higher in patients with B-cell NHL (707.7±155.4) than healthy donors (414.2±28.32, P=0.0119). There was no significant difference, however, in the absolute number of monocytes among different histological types of lymphoma (Figure 1b). There was also no significant difference of absolute numbers of myeloid-derived suppressor cells, T cells and natural killer T cells between lymphoma patients and healthy donors (data not shown).


IL-10 induces the development of immunosuppressive CD14(+)HLA-DR(low/-) monocytes in B-cell non-Hodgkin lymphoma.

Xiu B, Lin Y, Grote DM, Ziesmer SC, Gustafson MP, Maas ML, Zhang Z, Dietz AB, Porrata LF, Novak AJ, Liang AB, Yang ZZ, Ansell SM - Blood Cancer J (2015)

Absolute numbers of monocytes are increased in B-cell NHL. (a and b) A graph showing absolute monocyte counts in blood from NHL patients and healthy donors (a) or patients with different histologies (b) measured by flow cytometry. DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma. One milliliter freshly drawn whole blood was stained with a panel of Abs and analyzed by flow cytometry. Absolute monocyte counts were calculated as the numbers of CD14+ cells per microliter of blood (NHL: n=22, Ctrl: n=26). (c) Representative plots showing coexpression of CD14 and CD16 in blood from a healthy donor. Classical monocytes: CD14++CD16−; intermediate monocytes: CD14++CD16+; non-classical monocytes: CD14+CD16++. (d) Graphs showing the absolute counts (upper panel) or percentages (lower panel) of classical, intermediate and non-classical monocytes (Mo) in blood from NHL patients and healthy donors measured by flow cytometry.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526782&req=5

fig1: Absolute numbers of monocytes are increased in B-cell NHL. (a and b) A graph showing absolute monocyte counts in blood from NHL patients and healthy donors (a) or patients with different histologies (b) measured by flow cytometry. DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma. One milliliter freshly drawn whole blood was stained with a panel of Abs and analyzed by flow cytometry. Absolute monocyte counts were calculated as the numbers of CD14+ cells per microliter of blood (NHL: n=22, Ctrl: n=26). (c) Representative plots showing coexpression of CD14 and CD16 in blood from a healthy donor. Classical monocytes: CD14++CD16−; intermediate monocytes: CD14++CD16+; non-classical monocytes: CD14+CD16++. (d) Graphs showing the absolute counts (upper panel) or percentages (lower panel) of classical, intermediate and non-classical monocytes (Mo) in blood from NHL patients and healthy donors measured by flow cytometry.
Mentions: To determine the role of immune cells in NHL, we first measured the numbers of mononuclear phagocytes (monocytes, myeloid-derived suppressor cells, macrophages, dendritic cells), T cells and natural killer T cells by flow cytometry in the peripheral blood from 22 newly diagnosed NHL patients, including diffuse large B-cell lymphoma (n=6), follicular lymphoma (n=7), mantle cell lymphoma (n=4) and marginal zone lymphoma (n=5), and healthy donors matched for age and gender (n=26). As shown in Figure 1a, the absolute numbers of CD14+ monocytes were higher in patients with B-cell NHL (707.7±155.4) than healthy donors (414.2±28.32, P=0.0119). There was no significant difference, however, in the absolute number of monocytes among different histological types of lymphoma (Figure 1b). There was also no significant difference of absolute numbers of myeloid-derived suppressor cells, T cells and natural killer T cells between lymphoma patients and healthy donors (data not shown).

Bottom Line: 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.We found that lymphoma B cells produce IL-10 and supernatants from cultured lymphoma cells increased the CD14(+)HLA-DR(low/-) population.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Hematology, Tongji Hospital, Tongji University, Shanghai, China [2] Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA.

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.

No MeSH data available.


Related in: MedlinePlus