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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-treated monocytes inhibit T-cell activation and proliferation. (a) Representative plots showing the expression of CD69 and CD25 on activated CD3+ T cells (Ta) cocultured with or without untreated or IL-10-treated monocytes (Mo) for 3 days. Expression of CD69 and CD25 on resting T cells (Tr) was measured and used as a control. (b) Summarization of CD69 or CD25 induction in Tr or Ta cocultured with or without untreated or IL-10-treated Mo for 3 days, n=5. (c and d) Representative histograms showing proliferation measured by CFSE staining of Tr or Ta cocultured with or without untreated or IL-10-treated Mo for 3 or 6 days. Proliferative capacity was expressed by calculating the number of CFSEdim cells. The results from multiple experiments were summarized in panel (d). The percentage change of CFSEdim cells in each group was expressed as fold change when compared with the group Ta alone, n=5. (e) Graph showing the percentage change of CFSEdim T cells treated with or without untreated or IL-10-treated Mo in the presence of αIL-10R Ab or isotype control for 3 or 6 days, n=2.
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fig6: IL-10-treated monocytes inhibit T-cell activation and proliferation. (a) Representative plots showing the expression of CD69 and CD25 on activated CD3+ T cells (Ta) cocultured with or without untreated or IL-10-treated monocytes (Mo) for 3 days. Expression of CD69 and CD25 on resting T cells (Tr) was measured and used as a control. (b) Summarization of CD69 or CD25 induction in Tr or Ta cocultured with or without untreated or IL-10-treated Mo for 3 days, n=5. (c and d) Representative histograms showing proliferation measured by CFSE staining of Tr or Ta cocultured with or without untreated or IL-10-treated Mo for 3 or 6 days. Proliferative capacity was expressed by calculating the number of CFSEdim cells. The results from multiple experiments were summarized in panel (d). The percentage change of CFSEdim cells in each group was expressed as fold change when compared with the group Ta alone, n=5. (e) Graph showing the percentage change of CFSEdim T cells treated with or without untreated or IL-10-treated Mo in the presence of αIL-10R Ab or isotype control for 3 or 6 days, n=2.

Mentions: Next we wanted to test the immune function of IL-10-induced CD4+HLA-DRlow/− monocytes. To do this, we determined the effect of IL-10-treated monocytes on activation and proliferation of T cells. CD14+ monocytes were pretreated with IL-10 for 24 h and then washed three times to remove residual IL-10 prior to coculture with CD4+ T cells. Expression of activation markers and proliferation of CD4+ T cells were measured by flow cytometry. Compared with resting T cells, activated T cells expressed high levels of CD69 and CD25 and addition of untreated monocytes result in a slight decrease in CD69- and CD25-expressing cells (Figure 6a). In contrast, when activated T cells were cocultured with IL-10-pretreated monocytes, the expression of CD69 and CD25 dramatically decreased (Figures 6a and b).


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-treated monocytes inhibit T-cell activation and proliferation. (a) Representative plots showing the expression of CD69 and CD25 on activated CD3+ T cells (Ta) cocultured with or without untreated or IL-10-treated monocytes (Mo) for 3 days. Expression of CD69 and CD25 on resting T cells (Tr) was measured and used as a control. (b) Summarization of CD69 or CD25 induction in Tr or Ta cocultured with or without untreated or IL-10-treated Mo for 3 days, n=5. (c and d) Representative histograms showing proliferation measured by CFSE staining of Tr or Ta cocultured with or without untreated or IL-10-treated Mo for 3 or 6 days. Proliferative capacity was expressed by calculating the number of CFSEdim cells. The results from multiple experiments were summarized in panel (d). The percentage change of CFSEdim cells in each group was expressed as fold change when compared with the group Ta alone, n=5. (e) Graph showing the percentage change of CFSEdim T cells treated with or without untreated or IL-10-treated Mo in the presence of αIL-10R Ab or isotype control for 3 or 6 days, n=2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: IL-10-treated monocytes inhibit T-cell activation and proliferation. (a) Representative plots showing the expression of CD69 and CD25 on activated CD3+ T cells (Ta) cocultured with or without untreated or IL-10-treated monocytes (Mo) for 3 days. Expression of CD69 and CD25 on resting T cells (Tr) was measured and used as a control. (b) Summarization of CD69 or CD25 induction in Tr or Ta cocultured with or without untreated or IL-10-treated Mo for 3 days, n=5. (c and d) Representative histograms showing proliferation measured by CFSE staining of Tr or Ta cocultured with or without untreated or IL-10-treated Mo for 3 or 6 days. Proliferative capacity was expressed by calculating the number of CFSEdim cells. The results from multiple experiments were summarized in panel (d). The percentage change of CFSEdim cells in each group was expressed as fold change when compared with the group Ta alone, n=5. (e) Graph showing the percentage change of CFSEdim T cells treated with or without untreated or IL-10-treated Mo in the presence of αIL-10R Ab or isotype control for 3 or 6 days, n=2.
Mentions: Next we wanted to test the immune function of IL-10-induced CD4+HLA-DRlow/− monocytes. To do this, we determined the effect of IL-10-treated monocytes on activation and proliferation of T cells. CD14+ monocytes were pretreated with IL-10 for 24 h and then washed three times to remove residual IL-10 prior to coculture with CD4+ T cells. Expression of activation markers and proliferation of CD4+ T cells were measured by flow cytometry. Compared with resting T cells, activated T cells expressed high levels of CD69 and CD25 and addition of untreated monocytes result in a slight decrease in CD69- and CD25-expressing cells (Figure 6a). In contrast, when activated T cells were cocultured with IL-10-pretreated monocytes, the expression of CD69 and CD25 dramatically decreased (Figures 6a and b).

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