CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset.
Natural killer (NK) cells are innate immune lymphocytes that express a heterogeneous repertoire of germline-encoded receptors and undergo a distinct pattern of maturation. CD57 is a marker of terminal differentiation on human CD8(+) T cells. Very few newborn or fetal NK cells express CD57; however, the frequency of CD57-bearing NK cells increases with age. We assessed the transcriptional, phenotypic, and functional differences between CD57(+) and CD57(-) NK cells within the CD56(dim) mature NK subset. CD57(+) NK cells express a repertoire of NK-cell receptors, suggestive of a more mature phenotype, and proliferate less when stimulated with target cells and/or cytokines. By contrast, a higher frequency of CD57(+) NK cells produced interferon-γ and demonstrated more potent lytic activity when these cells were stimulated through the activating receptor CD16; however, they are less responsive to stimulation by interleukin-12 and interleukin-18. Finally, CD57 expression is induced on CD57(-)CD56(dim) NK cells after activation by interleukin-2. A combination of a mature phenotype, a higher cytotoxic capacity, a higher sensitivity to stimulation via CD16, with a decreased responsiveness to cytokines, and a decreased capacity to proliferate suggest that CD57(+) NK cells are highly mature and might be terminally differentiated.
Lopez-Vergès
Sandra
S
Department of Microbiology and Immunology and the Cancer Research Institute, University of California-San Francisco, San Francisco, CA 94143, USA.
Milush
Jeffrey M
JM
Pandey
Suchitra
S
York
Vanessa A
VA
Arakawa-Hoyt
Janice
J
Pircher
Hanspeter
H
Norris
Philip J
PJ
Nixon
Douglas F
DF
Lanier
Lewis L
LL
D000328:Adult; D019002:CD56 Antigen / Q000378:metabolism*; D018959:CD57 Antigens / Q000378:metabolism*; D016923:Cell Death; D002454:Cell Differentiation; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D058851:GPI-Linked Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology; D020382:Interleukin-18 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000145:classification* / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D017452:Receptors, IgG / Q000378:metabolism*
D019002:CD56 Antigen; D018959:CD57 Antigens; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D020382:Interleukin-18; C522918:NCAM1 protein, human; D017452:Receptors, IgG; D018664:Interleukin-12; D007371:Interferon-gamma