Expression patterns of NKG2A, KIR, and CD57 define a process of CD56dim NK-cell differentiation uncoupled from NK-cell education.
Natural killer (NK) cells are lymphocytes of the innate immune system that, following differentiation from CD56(bright) to CD56(dim) cells, have been thought to retain fixed functional and phenotypic properties throughout their lifespan. In contrast to this notion, we here show that CD56(dim) NK cells continue to differentiate. During this process, they lose expression of NKG2A, sequentially acquire inhibitory killer cell inhibitory immunoglobulin-like receptors and CD57, change their expression patterns of homing molecules, and display a gradual decline in proliferative capacity. All cellular intermediates of this process are represented in varying proportions at steady state and appear, over time, during the reconstitution of the immune system, as demonstrated in humanized mice and in patients undergoing hematopoietic stem cell transplantation. CD56(dim) NK-cell differentiation, and the associated functional imprint, occurs independently of NK-cell education by interactions with self-human leukocyte antigen class I ligands and is an essential part of the formation of human NK-cell repertoires.
Björkström
Niklas K
NK
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Riese
Peggy
P
Heuts
Frank
F
Andersson
Sandra
S
Fauriat
Cyril
C
Ivarsson
Martin A
MA
Björklund
Andreas T
AT
Flodström-Tullberg
Malin
M
Michaëlsson
Jakob
J
Rottenberg
Martin E
ME
Guzmán
Carlos A
CA
Ljunggren
Hans-Gustaf
HG
Malmberg
Karl-Johan
KJ
D000818:Animals; D019002:CD56 Antigen / Q000378:metabolism*; D018959:CD57 Antigens / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000378:metabolism*; D010641:Phenotype; D054340:Receptors, KIR / Q000378:metabolism*; D014183:Transplantation, Heterologous
D019002:CD56 Antigen; D018959:CD57 Antigens; C527054:KLRC1 protein, human; C522918:NCAM1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054340:Receptors, KIR