Distribution of subsets of blood monocytic cells throughout life

To the Editor: Currently, it is well established that monocytes are a heterogeneous type of cell consisting of phenotypically and functionally distinct subpopulations found to be numerically altered in blood in patients with a wide variety of disease conditions, such as infection, autoimmunity, respiratory and cardiovascular diseases, and inflammatory disorders.1,2 Thus, 3 subpopulations of circulating monocytic cells have been identified based on expression of the CD14 LPS receptor and the CD16 low-affinity Fc IgG receptor: (1) CD14hiCD16− classical monocytes (cMos), (2) CD14hiCD16+ intermediate monocytes (iMos), and (3) CD14−/loCD16+ nonclassical monocytes (ncMos).3 Monocytes circulate in blood for up to 3 days until recruited to virtually any human tissue, where they differentiate into either tissue macrophages or myeloid dendritic cells.4 Then, tissue macrophages can migrate from their tissue location through the lymph system5 before they potentially die outside the circulation.6 Despite our knowledge of the biology of monocytes increasing in recent years, normal reference ranges for the distinct monocyte subsets in blood throughout life (eg, from cord blood [CB] and newborns to elderly subjects) have never been systematically defined. [...]the precise maturational and functional relationship between the distinct populations of blood monocytes and their tissue distribution profiles remains unknown. 8 Based on the overall pattern of distribution of monocytic subsets in blood, with sequential peaks for cMos, iMos, and ncMos, particularly during the earliest periods of life and after the age of 50 years, our results would support the notion that iMos and ncMos might correspond to monocytic cell subsets at more advanced stages of maturation than cMos, which is also in accordance with previous reports.9 Whether such maturation occurs in blood or outside the bloodstream is still a subject of debate, although some reports support the notion that the differentiation steps of cMos into iMos and ncMos more likely occur outside the blood compartment rather than in the blood.6,9 To gain insight into the potential tissue relationship between cMos and both iMos and ncMos, we further investigated the distribution of the distinct subsets of monocytes in normal BM, lymph node, and spleen samples. [...]although CD62L+ cMos were by far the most abundant subset of cMos in blood and BM, they were outnumbered by CD62L− cMos in lymph node and spleen. [...]higher percentages