CD62L expression identifies a unique subset of polyfunctional CD56dim NK cells.
Human natural killer (NK) cells comprise 2 main subsets, CD56(bright) and CD56(dim) cells, that differ in function, phenotype, and tissue localization. To further dissect the heterogeneity of CD56(dim) cells, we have performed transcriptome analysis and functional ex vivo characterization of human NK-cell subsets according to the expression of markers related to differentiation, migration or competence. Here, we show for the first time that the ability to respond to cytokines or to activating receptors is mutually exclusive in almost all NK cells with the exception of CD56(dim) CD62L(+) cells. Indeed, only these cells combine the ability to produce interferon-gamma after cytokines and proliferate in vivo during viral infection with the capacity to kill and produce cytokines upon engagement of activating receptors. Therefore, CD56(dim) CD62L(+) cells represent a unique subset of polyfunctional NK cells. Ex vivo analysis of their function, phenotype, telomere length, frequencies during ageing as well as transfer experiments of NK-cell subsets into immunodeficient mice suggest that CD56(dim) CD62L(+) cells represent an intermediate stage of NK-cell maturation, which after restimulation can accomplish multiple tasks and further develop into terminally differentiated effectors.
Juelke
Kerstin
K
Innate Immunity, Deutsches Rheuma Forschungszentrum (DRFZ), Berlin, Germany.
Killig
Monica
M
Luetke-Eversloh
Merlin
M
Parente
Eliana
E
Gruen
Joachim
J
Morandi
Barbara
B
Ferlazzo
Guido
G
Thiel
Andreas
A
Schmitt-Knosalla
Isabela
I
Romagnani
Chiara
C
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D019002:CD56 Antigen / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D019041:L-Selectin / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020411:Oligonucleotide Array Sequence Analysis; D019707:Receptors, Chemokine / Q000378:metabolism; D016615:Telomere / Q000502:physiology; D014916:Whole-Body Irradiation
D015415:Biomarkers; D019002:CD56 Antigen; D016207:Cytokines; D019707:Receptors, Chemokine; D019041:L-Selectin; D007371:Interferon-gamma