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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

Lymphoma cells produce IL-10 and induce the development of CD14+HLA-DRlow/− monocytes. (a and b) Graphs showing IL-10 concentration in culture supernatant of MNCs from lymphoma tissues (a) or lymphoma cell lines (b). IL-10 concentration was measured by ELISA. (c and d) Representative plots showing HLA-DR expression on CD14+ cells cultured with or without supernatant of lymphoma cells (c) or SuDHL-2 cells (d). (e) Representative plots showing HLA-DR expression on CD14+ cells treated with or without IL-10 in the presence of αIL-10R Ab or isotype control. The percentage of CD14+HLA-DRlow/− cells from above experiment setting was summarized in the graph below (n=3). (f) Graph showing the percentage of HLA-DRlow/− cells in CD14+ monocytes cultured with or without supernatant from SuDHL-2 cells in the presence of αIL-10R Ab or isotype control (n=3).
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fig5: Lymphoma cells produce IL-10 and induce the development of CD14+HLA-DRlow/− monocytes. (a and b) Graphs showing IL-10 concentration in culture supernatant of MNCs from lymphoma tissues (a) or lymphoma cell lines (b). IL-10 concentration was measured by ELISA. (c and d) Representative plots showing HLA-DR expression on CD14+ cells cultured with or without supernatant of lymphoma cells (c) or SuDHL-2 cells (d). (e) Representative plots showing HLA-DR expression on CD14+ cells treated with or without IL-10 in the presence of αIL-10R Ab or isotype control. The percentage of CD14+HLA-DRlow/− cells from above experiment setting was summarized in the graph below (n=3). (f) Graph showing the percentage of HLA-DRlow/− cells in CD14+ monocytes cultured with or without supernatant from SuDHL-2 cells in the presence of αIL-10R Ab or isotype control (n=3).

Mentions: Given the elevated IL-10 serum levels in B-cell NHL patients, we then examined the ability of lymphoma cells to produce IL-10. Freshly isolated MNCs from lymphoma biopsy specimens were cultured in the presence of lipopolysaccharide for 24 h. The culture supernatants were collected and IL-10 levels were measured by ELISA. As shown in Figure 5a, lipopolysaccharide-activated MNCs from patient biopsy specimens produced a substantial amount of IL-10. Using lymphoma B-cell lines, we found that lymphoma cells were able to secret IL-10 variably with a very high amount of IL-10 produced by SuDHL-2 cells (Figure 5b). These results suggest that lymphoma B cells produce IL-10, with patient-to-patient variation and cell-line-dependent heterogeneity.


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)

Lymphoma cells produce IL-10 and induce the development of CD14+HLA-DRlow/− monocytes. (a and b) Graphs showing IL-10 concentration in culture supernatant of MNCs from lymphoma tissues (a) or lymphoma cell lines (b). IL-10 concentration was measured by ELISA. (c and d) Representative plots showing HLA-DR expression on CD14+ cells cultured with or without supernatant of lymphoma cells (c) or SuDHL-2 cells (d). (e) Representative plots showing HLA-DR expression on CD14+ cells treated with or without IL-10 in the presence of αIL-10R Ab or isotype control. The percentage of CD14+HLA-DRlow/− cells from above experiment setting was summarized in the graph below (n=3). (f) Graph showing the percentage of HLA-DRlow/− cells in CD14+ monocytes cultured with or without supernatant from SuDHL-2 cells in the presence of αIL-10R Ab or isotype control (n=3).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Lymphoma cells produce IL-10 and induce the development of CD14+HLA-DRlow/− monocytes. (a and b) Graphs showing IL-10 concentration in culture supernatant of MNCs from lymphoma tissues (a) or lymphoma cell lines (b). IL-10 concentration was measured by ELISA. (c and d) Representative plots showing HLA-DR expression on CD14+ cells cultured with or without supernatant of lymphoma cells (c) or SuDHL-2 cells (d). (e) Representative plots showing HLA-DR expression on CD14+ cells treated with or without IL-10 in the presence of αIL-10R Ab or isotype control. The percentage of CD14+HLA-DRlow/− cells from above experiment setting was summarized in the graph below (n=3). (f) Graph showing the percentage of HLA-DRlow/− cells in CD14+ monocytes cultured with or without supernatant from SuDHL-2 cells in the presence of αIL-10R Ab or isotype control (n=3).
Mentions: Given the elevated IL-10 serum levels in B-cell NHL patients, we then examined the ability of lymphoma cells to produce IL-10. Freshly isolated MNCs from lymphoma biopsy specimens were cultured in the presence of lipopolysaccharide for 24 h. The culture supernatants were collected and IL-10 levels were measured by ELISA. As shown in Figure 5a, lipopolysaccharide-activated MNCs from patient biopsy specimens produced a substantial amount of IL-10. Using lymphoma B-cell lines, we found that lymphoma cells were able to secret IL-10 variably with a very high amount of IL-10 produced by SuDHL-2 cells (Figure 5b). These results suggest that lymphoma B cells produce IL-10, with patient-to-patient variation and cell-line-dependent heterogeneity.

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