AbstractThe 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.