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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

Phenotype of CD14+HLA-DRlow/− or HLA-DR+ monocytes in B-cell NHL. A 10-color flow cytometry was employed to determine the expression of surface markers included CD86, CD64, CD32, CD80, CD142, TNFR2, CD40, B7-H1, PD-1, CD206, CD163 and CD169 on CD14+HLA-DRlow/− or CD14+HLA-DR+ monocytes from both healthy donors (NC) or lymphoma patients (NHL).
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fig3: Phenotype of CD14+HLA-DRlow/− or HLA-DR+ monocytes in B-cell NHL. A 10-color flow cytometry was employed to determine the expression of surface markers included CD86, CD64, CD32, CD80, CD142, TNFR2, CD40, B7-H1, PD-1, CD206, CD163 and CD169 on CD14+HLA-DRlow/− or CD14+HLA-DR+ monocytes from both healthy donors (NC) or lymphoma patients (NHL).

Mentions: Next we determined the phenotype of CD14+HLA-DRlow/− monocytes from B-cell NHL patients by using 10-color flow cytometry. Markers analyzed included CD80, CD86, CD64, CD32, CD163, CD169, CD206, TNFR2, CD40, B7-H1, PD-1, and CD142. As shown in Figure 3, both CD14+HLA-DR+ and CD14+HLA-DRlow/− monocytes expressed some of these markers, including CD86 and CD64. However, the expression of these cell surface markers was generally lower in HLA-DRlow/− cells compared with HLA-DR+ monocytes, although some of these surface markers were expressed at a low level on both HLA-DRlow/− and HLA-DR+ cells. There was no difference in the profile of cell surface markers when HLA-DRlow/− and HLA-DR+ populations were compared between lymphoma patients and healthy individuals. We did, however, observe a difference of B7-H1 expression between HLA-DR+ and HLA-DRlow monocytes in normal controls but not in lymphoma patients based on the P-value. However, B7-H1 expression on monocytes was very low in both normal controls and NHL patients. This finding may therefore have limited biological significance. Overall, our findings suggest that HLA-DRlow/− monocytes are in fact a physiological population that is expanded in lymphoma patients.


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)

Phenotype of CD14+HLA-DRlow/− or HLA-DR+ monocytes in B-cell NHL. A 10-color flow cytometry was employed to determine the expression of surface markers included CD86, CD64, CD32, CD80, CD142, TNFR2, CD40, B7-H1, PD-1, CD206, CD163 and CD169 on CD14+HLA-DRlow/− or CD14+HLA-DR+ monocytes from both healthy donors (NC) or lymphoma patients (NHL).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Phenotype of CD14+HLA-DRlow/− or HLA-DR+ monocytes in B-cell NHL. A 10-color flow cytometry was employed to determine the expression of surface markers included CD86, CD64, CD32, CD80, CD142, TNFR2, CD40, B7-H1, PD-1, CD206, CD163 and CD169 on CD14+HLA-DRlow/− or CD14+HLA-DR+ monocytes from both healthy donors (NC) or lymphoma patients (NHL).
Mentions: Next we determined the phenotype of CD14+HLA-DRlow/− monocytes from B-cell NHL patients by using 10-color flow cytometry. Markers analyzed included CD80, CD86, CD64, CD32, CD163, CD169, CD206, TNFR2, CD40, B7-H1, PD-1, and CD142. As shown in Figure 3, both CD14+HLA-DR+ and CD14+HLA-DRlow/− monocytes expressed some of these markers, including CD86 and CD64. However, the expression of these cell surface markers was generally lower in HLA-DRlow/− cells compared with HLA-DR+ monocytes, although some of these surface markers were expressed at a low level on both HLA-DRlow/− and HLA-DR+ cells. There was no difference in the profile of cell surface markers when HLA-DRlow/− and HLA-DR+ populations were compared between lymphoma patients and healthy individuals. We did, however, observe a difference of B7-H1 expression between HLA-DR+ and HLA-DRlow monocytes in normal controls but not in lymphoma patients based on the P-value. However, B7-H1 expression on monocytes was very low in both normal controls and NHL patients. This finding may therefore have limited biological significance. Overall, our findings suggest that HLA-DRlow/− monocytes are in fact a physiological population that is expanded in lymphoma patients.

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