M: Circulating CD14-CD36+ peripheral blood mononuclear cells constitutively produce interleukin-10

Abstract: The impact of immune regulatory im-balance covers surprising physiological breadth. Although dominance of anti-inflammatory cyto-kines such as IL-10 is associated with reduced im-mune responsiveness and susceptibility to persis-tent infection, conditions such as cardiovascular disease and diabetes are linked to chronic inflam-mation and lower IL-10 levels. An appropriate threshold for immune activation is critical for op-timal protection from infection and conversely, from short- and long-term side-effects of immune effector mechanisms. To assess the possibility that IL-10 plays a role in setting this threshold and that healthy maintenance of immune silence may in-volve low-level immune suppression, we sought out and characterized human peripheral blood cells constitutively producing the immunosuppressive cytokine IL-10. We determined the surface pheno-type of circulating PBMC constitutively producing IL-10 by surface and intracellular flow cytometry and visualized their ultrastructure by electron mi-croscopy. The frequency of IL-10-producing and-secreting cells was estimated by ELISPOT and flow cytometry. Up to 1 % of PBMC constitutively produce IL-10. These CD14–CD36CD61 non-adherent cells expressed general markers of hema-topoietic and progenitor cells (CD45 and CD7) but no stem cell, T cell, B cell, NK cell, monocytes or dendritic cell markers. Inflammation-associated TLRs were also absent. The IL-10-producing cells had prominent nuclei, multiple mitochondria, and abundant rough endoplasmic reticulum. Healthy individuals have PBMC constitutively producing IL-10. Although the lineage of these cells remains unclear, their properties and frequency suggest a potential role in homeostatic or innate immune suppression. J. Leukoc. Biol. 82: 152–160; 2007. Key Words: immune regulation hematopoietic cells cytokine