AUTHOR=Melsen Janine E. , Lugthart Gertjan , Lankester Arjan C. , Schilham Marco W. TITLE=Human Circulating and Tissue-Resident CD56bright Natural Killer Cell Populations JOURNAL=Frontiers in Immunology VOLUME=7 YEAR=2016 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00262 DOI=10.3389/fimmu.2016.00262 ISSN=1664-3224 ABSTRACT=

Two human natural killer (NK) cell subsets are usually distinguished, displaying the CD56^dimCD16⁺ and the CD56^brightCD16^−/+ phenotype. This distinction is based on NK cells present in blood, where the CD56^dim NK cells predominate. However, CD56^bright NK cells outnumber CD56^dim NK cells in the human body due to the fact that they are predominant in peripheral and lymphoid tissues. Interestingly, within the total CD56^bright NK cell compartment, a major phenotypical and functional diversity is observed, as demonstrated by the discovery of tissue-resident CD56^bright NK cells in the uterus, liver, and lymphoid tissues. Uterus-resident CD56^bright NK cells express CD49a while the liver- and lymphoid tissue-resident CD56^bright NK cells are characterized by co-expression of CD69 and CXCR6. Tissue-resident CD56^bright NK cells have a low natural cytotoxicity and produce little interferon-γ upon monokine stimulation. Their distribution and specific phenotype suggest that the tissue-resident CD56^bright NK cells exert tissue-specific functions. In this review, we examine the CD56^bright NK cell diversity by discussing the distribution, phenotype, and function of circulating and tissue-resident CD56^bright NK cells. In addition, we address the ongoing debate concerning the developmental relationship between circulating CD56^bright and CD56^dim NK cells and speculate on the position of tissue-resident CD56^bright NK cells. We conclude that distinguishing tissue-resident CD56^bright NK cells from circulating CD56^bright NK cells is a prerequisite for the better understanding of the specific role of CD56^bright NK cells in the complex process of human immune regulation.