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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

IL-10 induces the development of CD14+HLA-DRlow/− monocytes. (a) Representative plots showing the expression of HLA-DR on CD14+ monocytes treated with or without IL-10 or IFN-γ in the presence or absence of M-CSF for 24 h. (b) Summarization of HLA-DR expression level in CD14+ monocytes treated with or without IL-10, IFN-γ, IL-4, M-CSF or GM-CSF. (c) Graph showing the percentage of HLA-DRlow/− cells of CD14+ monocytes treated with IL-10 at escalating doses. (d) Graph showing serum IL-10 level in healthy donors or patients with B-cell NHL. IL-10 concentration was measured by multiplex ELISA (Luminex). (e) Graph showing absolute monocyte counts (AMC)/μl in lymphoma patients with undetectable (<20 pg/ml, n=118) or detectable (>20 pg/ml, n=101) IL-10 serum levels. (f) Representative histograms showing the expression of IL-10Rα or IL-10Rβ on CD14+ monocytes in patients with B-cell NHL.
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fig4: IL-10 induces the development of CD14+HLA-DRlow/− monocytes. (a) Representative plots showing the expression of HLA-DR on CD14+ monocytes treated with or without IL-10 or IFN-γ in the presence or absence of M-CSF for 24 h. (b) Summarization of HLA-DR expression level in CD14+ monocytes treated with or without IL-10, IFN-γ, IL-4, M-CSF or GM-CSF. (c) Graph showing the percentage of HLA-DRlow/− cells of CD14+ monocytes treated with IL-10 at escalating doses. (d) Graph showing serum IL-10 level in healthy donors or patients with B-cell NHL. IL-10 concentration was measured by multiplex ELISA (Luminex). (e) Graph showing absolute monocyte counts (AMC)/μl in lymphoma patients with undetectable (<20 pg/ml, n=118) or detectable (>20 pg/ml, n=101) IL-10 serum levels. (f) Representative histograms showing the expression of IL-10Rα or IL-10Rβ on CD14+ monocytes in patients with B-cell NHL.

Mentions: To identify which cytokine may be involved in the expansion of CD14+HLA-DRlow/− monocytes in B-cell NHL, we tested a panel of cytokines for their ability to decrease HLA-DR expression on CD14+ monocytes. We treated monocytes from peripheral blood of healthy donors with IL-10, IL-4, IFN-γ, GM-CSF and M-CSF alone or in combination for 24 h and then measured HLA-DR expression. As shown in Figure 4a, the majority of untreated CD14+ monocytes had HLA-DR expression on cell surface and the number of HLA-DRlow/− cells was low. Treatment of CD14+ monocytes with IL-10, however, decreased HLA-DR expression and increased the number of CD14+HLA-DRlow/− cells. As a control, IFN-γ treatment strongly enhanced the expression of HLA-DR on CD14+ monocytes and resulted in a disappearance of CD14+HLA-DRlow/− cells. Similar treatment with multiple cytokines found that IL-10 remained the only cytokine that significantly downregulated the HLA-DR expression on CD14+ monocytes (Figure 4b). We then confirmed that IL-10 induced the development of CD14+HLA-DRlow/− cells in a dose-dependent manner (Figure 4c).


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)

IL-10 induces the development of CD14+HLA-DRlow/− monocytes. (a) Representative plots showing the expression of HLA-DR on CD14+ monocytes treated with or without IL-10 or IFN-γ in the presence or absence of M-CSF for 24 h. (b) Summarization of HLA-DR expression level in CD14+ monocytes treated with or without IL-10, IFN-γ, IL-4, M-CSF or GM-CSF. (c) Graph showing the percentage of HLA-DRlow/− cells of CD14+ monocytes treated with IL-10 at escalating doses. (d) Graph showing serum IL-10 level in healthy donors or patients with B-cell NHL. IL-10 concentration was measured by multiplex ELISA (Luminex). (e) Graph showing absolute monocyte counts (AMC)/μl in lymphoma patients with undetectable (<20 pg/ml, n=118) or detectable (>20 pg/ml, n=101) IL-10 serum levels. (f) Representative histograms showing the expression of IL-10Rα or IL-10Rβ on CD14+ monocytes in patients with B-cell NHL.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig4: IL-10 induces the development of CD14+HLA-DRlow/− monocytes. (a) Representative plots showing the expression of HLA-DR on CD14+ monocytes treated with or without IL-10 or IFN-γ in the presence or absence of M-CSF for 24 h. (b) Summarization of HLA-DR expression level in CD14+ monocytes treated with or without IL-10, IFN-γ, IL-4, M-CSF or GM-CSF. (c) Graph showing the percentage of HLA-DRlow/− cells of CD14+ monocytes treated with IL-10 at escalating doses. (d) Graph showing serum IL-10 level in healthy donors or patients with B-cell NHL. IL-10 concentration was measured by multiplex ELISA (Luminex). (e) Graph showing absolute monocyte counts (AMC)/μl in lymphoma patients with undetectable (<20 pg/ml, n=118) or detectable (>20 pg/ml, n=101) IL-10 serum levels. (f) Representative histograms showing the expression of IL-10Rα or IL-10Rβ on CD14+ monocytes in patients with B-cell NHL.
Mentions: To identify which cytokine may be involved in the expansion of CD14+HLA-DRlow/− monocytes in B-cell NHL, we tested a panel of cytokines for their ability to decrease HLA-DR expression on CD14+ monocytes. We treated monocytes from peripheral blood of healthy donors with IL-10, IL-4, IFN-γ, GM-CSF and M-CSF alone or in combination for 24 h and then measured HLA-DR expression. As shown in Figure 4a, the majority of untreated CD14+ monocytes had HLA-DR expression on cell surface and the number of HLA-DRlow/− cells was low. Treatment of CD14+ monocytes with IL-10, however, decreased HLA-DR expression and increased the number of CD14+HLA-DRlow/− cells. As a control, IFN-γ treatment strongly enhanced the expression of HLA-DR on CD14+ monocytes and resulted in a disappearance of CD14+HLA-DRlow/− cells. Similar treatment with multiple cytokines found that IL-10 remained the only cytokine that significantly downregulated the HLA-DR expression on CD14+ monocytes (Figure 4b). We then confirmed that IL-10 induced the development of CD14+HLA-DRlow/− cells in a dose-dependent manner (Figure 4c).

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