CD56brightCD16- killer Ig-like receptor- NK cells display longer telomeres and acquire features of CD56dim NK cells upon activation.
Human NK cells can be divided into CD56(dim)CD16(+) killer Ig-like receptors (KIR)(+/-) and CD56(bright)CD16(-) KIR(-) subsets that have been characterized extensively regarding their different functions, phenotype, and tissue localization. Nonetheless, the developmental relationship between these two NK cell subsets remains controversial. We report that, upon cytokine activation, peripheral blood (PB)-CD56(bright) NK cells mainly gain the signature of CD56(dim) NK cells. Remarkably, KIR can be induced not only on CD56(bright), but also on CD56(dim) KIR(-) NK cells, and their expression correlates with lower proliferative response. In addition, we demonstrate for the first time that PB-CD56(dim) display shorter telomeres than PB- and lymph node (LN)-derived CD56(bright) NK cells. Along this line, although human NK cells collected from nonreactive LN display almost no KIR and CD16 expression, NK cells derived from highly reactive LN, efferent lymph, and PB express significant amounts of KIR and CD16, implying that CD56(bright) NK cells could acquire these molecules in the LN during inflammation and then circulate through the efferent lymph into PB as KIR(+)CD16(+) NK cells. Altogether, our results suggest that CD56(bright)CD16(-) KIR(-) and CD56(dim)CD16(+)KIR(+/-) NK cells correspond to sequential steps of differentiation and support the hypothesis that secondary lymphoid organs can be sites of NK cell final maturation and self-tolerance acquisition during immune reaction.
Romagnani
Chiara
C
Department of Clinical Immunology, German Rheumatism Research Centre, Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany.
Juelke
Kerstin
K
Falco
Michela
M
Morandi
Barbara
B
D'Agostino
Antonella
A
Costa
Roberta
R
Ratto
Giovanni
G
Forte
Giuseppe
G
Carrega
Paolo
P
Lui
Gabrielle
G
Conte
Romana
R
Strowig
Till
T
Moretta
Alessandro
A
Münz
Christian
C
Thiel
Andreas
A
Moretta
Lorenzo
L
Ferlazzo
Guido
G
D019002:CD56 Antigen / Q000032:analysis*; D002478:Cells, Cultured; D006801:Humans; D006965:Hyperplasia; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D017452:Receptors, IgG / Q000032:analysis*; D011971:Receptors, Immunologic / Q000032:analysis*; D054340:Receptors, KIR; D017634:Self Tolerance; D016615:Telomere
D019002:CD56 Antigen; D019409:Interleukin-15; D007376:Interleukin-2; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D018664:Interleukin-12