Circulating CD14-CD36+ peripheral blood mononuclear cells constitutively produce interleukin-10.
The impact of immune regulatory imbalance covers surprising physiological breadth. Although dominance of anti-inflammatory cytokines such as IL-10 is associated with reduced immune responsiveness and susceptibility to persistent infection, conditions such as cardiovascular disease and diabetes are linked to chronic inflammation and lower IL-10 levels. An appropriate threshold for immune activation is critical for optimal 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 involve low-level immune suppression, we sought out and characterized human peripheral blood cells constitutively producing the immunosuppressive cytokine IL-10. We determined the surface phenotype of circulating PBMC constitutively producing IL-10 by surface and intracellular flow cytometry and visualized their ultrastructure by electron microscopy. 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(-)CD36(+)CD61(+) nonadherent cells expressed general markers of hematopoietic 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.
Barrett
Lisa
L
Immunology Program, Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Dai
Chunming
C
Gamberg
Jane
J
Gallant
Maureen
M
Grant
Michael
M
D000328:Adult; D001773:Blood Cells; D001775:Blood Circulation; D018955:CD36 Antigens / Q000032:analysis*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D039661:Integrin beta3 / Q000032:analysis; D016753:Interleukin-10 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000648:ultrastructure; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D051193:Toll-Like Receptors / Q000032:analysis
D018955:CD36 Antigens; D039661:Integrin beta3; D018950:Lipopolysaccharide Receptors; D051193:Toll-Like Receptors; D016753:Interleukin-10