IL-10 induces the development of immunosuppressive CD14(+)HLA-DR(low/-) monocytes in B-cell non-Hodgkin lymphoma.

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.

• Authors: B Xiu, Y Lin, D M Grote, S C Ziesmer, M P Gustafson, M L Maas, Z Zhang, A B Dietz, L F Porrata, A J Novak, A-B Liang, Z-Z Yang, S M Ansell
• Journal: Blood cancer journal (Blood Cancer J) Vol. 5 Pg. e328 (Jul 31 2015) ISSN: 2044-5385 [Electronic] United States
• PMID: 26230952 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-DR Antigens
• IL10 protein, human
• Lipopolysaccharide Receptors
• Interleukin-10

Topics

• B-Lymphocytes (metabolism)
• Case-Control Studies
• Cell Proliferation
• Cells, Cultured
• HLA-DR Antigens (metabolism)
• Humans
• Immune Tolerance
• Interleukin-10 (physiology)
• Lipopolysaccharide Receptors (metabolism)
• Lymphocyte Activation
• Lymphoma, Non-Hodgkin (blood, immunology)
• Monocytes (metabolism)
• T-Lymphocytes (immunology, metabolism)