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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

Monocytes from B-cell NHL exhibit CD14+HLA-DRlow/− phenotype. (a) Representative plots showing coexpression of CD14 and HLA-DR in blood from healthy donors (Ctrl) and lymphoma patients (NHL). CD14+HLA-DRlow/− cells were defined based on isotype control gate. (b) Graphs showing absolute counts (left) or the percentage (right) of CD14+HLA-DRlow/− cells in blood from NHL patients and healthy donors measured by flow cytometry. (c) Graphs showing expression level of HLA-DR on classical, intermediate and non-classical monocytes in blood from NHL patients and healthy donors. (d) A graph showing the percentage of CD14+HLA-DRlow/− monocytes in blood from NHL patients with different histologies. (e) Graphs showing the percentage of CD14+HLA-DRlow/− monocytes in blood from NHL patients with different International Prognostic Index (IPI) scores.
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fig2: Monocytes from B-cell NHL exhibit CD14+HLA-DRlow/− phenotype. (a) Representative plots showing coexpression of CD14 and HLA-DR in blood from healthy donors (Ctrl) and lymphoma patients (NHL). CD14+HLA-DRlow/− cells were defined based on isotype control gate. (b) Graphs showing absolute counts (left) or the percentage (right) of CD14+HLA-DRlow/− cells in blood from NHL patients and healthy donors measured by flow cytometry. (c) Graphs showing expression level of HLA-DR on classical, intermediate and non-classical monocytes in blood from NHL patients and healthy donors. (d) A graph showing the percentage of CD14+HLA-DRlow/− monocytes in blood from NHL patients with different histologies. (e) Graphs showing the percentage of CD14+HLA-DRlow/− monocytes in blood from NHL patients with different International Prognostic Index (IPI) scores.

Mentions: To further define the phenotype of peripheral blood monocytes in B-cell NHL patients, we measured the expression of a panel of surface markers. Expression of most surface markers such as CD80, CD86, CD206, CD163, CD40, PD-1, B7-H1, CD169 and CD142 showed no significant difference between patients and healthy donors (data not shown). However, we observed that the surface expression level of HLA-DR on CD14+ monocytes was decreased in lymphoma patients compared with healthy donors (Figure 2a), resulting in an increased population of CD14+HLA-DRlow/− monocytes. Supporting this finding, we found that the absolute numbers and percentages of CD14+HLA-DRlow/− monocytes were significantly higher in lymphoma patients than in healthy donors (Figure 2b). Furthermore, the increased population of CD14+HLA-DRlow/− cells came mainly from the classical monocyte population in both lymphoma patients and healthy donors (Figure 2c). We found that there was no significant difference in the percentage of HLA-DRlow monocytes among the subtypes of lymphoma, although there seemed to be with a higher percentage of HLA-DRlow monocytes in patients with mantle cell lymphoma or marginal zone lymphoma (Figure 2d). Small sample numbers in each histology group may, however, account for this negative finding. Although the numbers of CD14+HLA-DRlow/− monocytes were not significantly different among the subtypes of lymphoma, patients with a higher International Prognostic Index score had statistically a higher percentage of CD14+HLA-DRlow/− monocytes (Figure 2e).


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)

Monocytes from B-cell NHL exhibit CD14+HLA-DRlow/− phenotype. (a) Representative plots showing coexpression of CD14 and HLA-DR in blood from healthy donors (Ctrl) and lymphoma patients (NHL). CD14+HLA-DRlow/− cells were defined based on isotype control gate. (b) Graphs showing absolute counts (left) or the percentage (right) of CD14+HLA-DRlow/− cells in blood from NHL patients and healthy donors measured by flow cytometry. (c) Graphs showing expression level of HLA-DR on classical, intermediate and non-classical monocytes in blood from NHL patients and healthy donors. (d) A graph showing the percentage of CD14+HLA-DRlow/− monocytes in blood from NHL patients with different histologies. (e) Graphs showing the percentage of CD14+HLA-DRlow/− monocytes in blood from NHL patients with different International Prognostic Index (IPI) scores.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Monocytes from B-cell NHL exhibit CD14+HLA-DRlow/− phenotype. (a) Representative plots showing coexpression of CD14 and HLA-DR in blood from healthy donors (Ctrl) and lymphoma patients (NHL). CD14+HLA-DRlow/− cells were defined based on isotype control gate. (b) Graphs showing absolute counts (left) or the percentage (right) of CD14+HLA-DRlow/− cells in blood from NHL patients and healthy donors measured by flow cytometry. (c) Graphs showing expression level of HLA-DR on classical, intermediate and non-classical monocytes in blood from NHL patients and healthy donors. (d) A graph showing the percentage of CD14+HLA-DRlow/− monocytes in blood from NHL patients with different histologies. (e) Graphs showing the percentage of CD14+HLA-DRlow/− monocytes in blood from NHL patients with different International Prognostic Index (IPI) scores.
Mentions: To further define the phenotype of peripheral blood monocytes in B-cell NHL patients, we measured the expression of a panel of surface markers. Expression of most surface markers such as CD80, CD86, CD206, CD163, CD40, PD-1, B7-H1, CD169 and CD142 showed no significant difference between patients and healthy donors (data not shown). However, we observed that the surface expression level of HLA-DR on CD14+ monocytes was decreased in lymphoma patients compared with healthy donors (Figure 2a), resulting in an increased population of CD14+HLA-DRlow/− monocytes. Supporting this finding, we found that the absolute numbers and percentages of CD14+HLA-DRlow/− monocytes were significantly higher in lymphoma patients than in healthy donors (Figure 2b). Furthermore, the increased population of CD14+HLA-DRlow/− cells came mainly from the classical monocyte population in both lymphoma patients and healthy donors (Figure 2c). We found that there was no significant difference in the percentage of HLA-DRlow monocytes among the subtypes of lymphoma, although there seemed to be with a higher percentage of HLA-DRlow monocytes in patients with mantle cell lymphoma or marginal zone lymphoma (Figure 2d). Small sample numbers in each histology group may, however, account for this negative finding. Although the numbers of CD14+HLA-DRlow/− monocytes were not significantly different among the subtypes of lymphoma, patients with a higher International Prognostic Index score had statistically a higher percentage of CD14+HLA-DRlow/− monocytes (Figure 2e).

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