Article

Functionally distinct subsets of human NK cells and monocyte/DC-like cells identified by coexpression of CD56, CD7, and CD4.

Division of Experimental Medicine, Department of Medicine, University of California, San Francisco;
Blood (impact factor: 9.9). 10/2009; 114(23):4823-31. DOI:10.1182/blood-2009-04-216374 pp.4823-31
Source: PubMed

ABSTRACT The lack of natural killer (NK) cell-specific markers, as well as the overlap among several common surface antigens and functional properties, has obscured the delineation between NK cells and dendritic cells. Here, novel subsets of peripheral blood CD3/14/19(neg) NK cells and monocyte/dendritic cell (DC)-like cells were identified on the basis of CD7 and CD4 expression. Coexpression of CD7 and CD56 differentiates NK cells from CD56+ monocyte/DC-like cells, which lack CD7. In contrast to CD7+CD56+ NK cells, CD7(neg)CD56+ cells lack expression of NK cell-associated markers, but share commonalities in their expression of various monocyte/DC-associated markers. Using CD7, we observed approximately 60% of CD4+CD56+ cells were CD7(neg) cells, indicating the actual frequency of activated CD4+ NK cells is much lower in the blood than previously recognized. Functionally, only CD7+ NK cells secrete gamma interferon (IFNgamma) and degranulate after interleukin-12 (IL-12) plus IL-18 or K562 target cell stimulation. Furthermore, using CD7 to separate CD56+ NK cells and CD56+ myeloid cells, we demonstrate that unlike resting CD7+CD56+ NK cells, the CD7(neg)CD56+ myeloid cells stimulate a potent allogeneic response. Our data indicate that CD7 and CD56 coexpression discriminates NK cells from CD7(neg)CD56+ monocyte/DC-like cells, thereby improving our ability to study the intricacies of NK-cell subset phenotypes and functions in vivo.

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Keywords

activated CD4+ NK cells
 
CD56 differentiates NK cells
 
CD56+ monocyte/DC-like cells
 
CD56+ myeloid cells
 
CD7(neg)CD56+ cells lack expression
 
CD7(neg)CD56+ monocyte/DC-like cells
 
CD7(neg)CD56+ myeloid cells stimulate
 
CD7+ NK cells secrete gamma interferon
 
common surface antigens
 
DC)-like cells
 
functional properties
 
K562 target cell stimulation
 
monocyte/dendritic cell
 
natural killer
 
NK cell-associated markers
 
NK cells
 
NK-cell subset phenotypes
 
potent allogeneic response
 
resting CD7+CD56+ NK cells
 
separate CD56+ NK cells