Phenotypic and functional heterogeneity of human NK cells developing after umbilical cord blood transplantation: a role for human cytomegalovirus?

Abstract

Natural killer (NK) cells play a crucial role in early immunity after hematopoietic stem cell transplantation because they are the first lymphocyte subset recovering after the allograft. In this study, we analyzed the development of NK cells after intrabone umbilical cord blood (CB) transplantation in 18 adult patients with hematologic malignancies. Our data indicate that, also in this transplantation setting, NK cells are the first lymphoid population detectable in peripheral blood.

Human Cytomegalovirus Infection Promotes Rapid Maturation of NK Cells Expressing Activating Killer Ig–like Receptor in Patients Transplanted with NKG2C−/− Umbilical Cord Blood

“…The statistical significance (p value) is indicated. Graphic representations and statistical analyses were performed using the PASW Statistics version 20.0 software (formerly SPSS Statistics, IBM) (17) and GraphPad Prism 6 (GraphPad Software, La Jolla, CA).…”

“…The medium used throughout the experiments was RPMI 1640 supplemented with 2 mM L-glutamine, 1% penicillin-streptomycin-neomycin mixture, and 10% heat-inactivated FCS (17).…”

“…Thus, in such patients, we detected a rapid development of highly differentiated NKG2A 2 KIR + NKG2C + NK cells that, similar to what we observed in HIV/HCMV-infected subjects (19), were characterized by marked downregulation of Siglec-7 and, to a lower extent, of CD56. Notably, these NK cell populations, expressing a memory-like surface phenotype, could contribute to protection against leukemia relapse and to control of infections after transplantation (17,18,20). In this context, a role for NKG2C + NK cells has been proposed in the resolution of HCMV infection in a T cell-deficient patient (21).…”

“…In this context, we and others (17,18) have previously shown that HCMV infection/reactivation can promote NK cell maturation in adult patients undergoing umbilical cord blood transplantation (UCBT) for high-risk leukemias. Thus, in such patients, we detected a rapid development of highly differentiated NKG2A 2 KIR + NKG2C + NK cells that, similar to what we observed in HIV/HCMV-infected subjects (19), were characterized by marked downregulation of Siglec-7 and, to a lower extent, of CD56.…”

Natural killer cell memory in infection, inflammation and cancer

“…This study suggested that, in analogy to the MCMV model, interactions between the CD94-NKG2C receptor and ligands on HCMV-infected cells might drive the generation of a memory NK cell subset. Subsequent studies of patients who were infected by HCMV or in whom the virus was reactivated owing to immunosuppression after solid organ or haematop oietic stem cell transplantation confirmed that the CD94-NKG2C + NK cell population preferentially expands during acute HCMV infection, subsequently persist as memory cells and can constitute up to 70% of the total NK cell population in some individuals [34][35][36] . Moreover, after haematopoietic stem cell transplantation, CD94-NKG2C + NK cells from HCMV-seropositive donors demonstrated enhanced function in response to re-exposure to HCMV in HCMV-seropositive recipients whereas CD94-NKG2C + NK cells from HCMVseronegative donors did not, suggesting the existence of a memory response against HCMV infection 37 .…”