Human cytomegalovirus infection promotes rapid maturation of NK cells expressing activating killer Ig-like receptor in patients transplanted with NKG2C-/- umbilical cord blood.
NK cells are the first lymphoid population recovering after allogeneic hematopoietic stem cell transplantation and play a crucial role in early immunity after the graft. Recently, it has been shown that human CMV (HCMV) infection/reactivation can deeply influence NK cell reconstitution after umbilical cord blood transplantation by accelerating the differentiation of mature NKG2A(-) killer Ig-like receptor (KIR)(+) NK cells characterized by the expression of the NKG2C-activating receptor. In view of the hypothesis that NKG2C could be directly involved in NK cell maturation driven by HCMV infection, we analyzed the maturation and function of NK cells developing in three patients with hematological malignancies given umbilical cord blood transplantation from donors carrying a homozygous deletion of the NKG2C gene. We show that HCMV infection can drive rapid NK maturation, characterized by the expansion of CD56(dim)NKG2A(-)KIR(+) cells, even in the absence of NKG2C expression. Interestingly, this expanded mature NK cell subset expressed surface-activating KIR that could trigger NK cell cytotoxicity, degranulation, and IFN-γ release. Given the absence of NKG2C, it is conceivable that activating KIRs may play a role in the HCMV-driven NK cell maturation and that NK cells expressing activating KIRs might contribute, at least in part, to the control of infections after transplantation.
Dipartimento di Medicina Sperimentale and Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, 16132 Genoa, Italy;
Mariella
M
Della Chiesa
Michela
M
Falco
Alice
A
Bertaina
Letizia
L
Muccio
Claudia
C
Alicata
Francesco
F
Frassoni
Franco
F
Locatelli
Lorenzo
L
Moretta
Alessandro
A
Moretta
D000328:Adult; D019002:CD56 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002648:Child; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology; D005312:Fetal Blood / Q000637:transplantation*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics / Q000378:metabolism*; D054340:Receptors, KIR / Q000378:metabolism; D054343:Receptors, KIR2DL2 / Q000378:metabolism; D054344:Receptors, KIR2DL3 / Q000378:metabolism; D054341:Receptors, KIR3DL1 / Q000378:metabolism; D054349:Receptors, KIR3DS1 / Q000378:metabolism
D019002:CD56 Antigen; C496212:KIR2DS1 protein, human; C527059:KLRC2 protein, human; C522918:NCAM1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1; D007371:Interferon-gamma