Adaptive Natural Killer Cell and Killer Cell Immunoglobulin-Like Receptor-Expressing T Cell Responses are Induced by Cytomegalovirus and Are Associated with Protection against Cytomegalovirus Reactivation after Allogeneic Donor Hematopoietic Cell Transplantation.
Cytomegalovirus (CMV) reactivates in >30% of CMV-seropositive patients after allogeneic hematopoietic cell transplantation (HCT). Previously, we reported an increase of natural killer (NK) cells expressing NKG2C, CD57, and inhibitory killer cell immunoglobulin-like receptors (KIRs) in response to CMV reactivation after HCT. These NK cells persist after the resolution of infection and display "adaptive" or memory properties. Despite these findings, the differential impact of persistent/inactive versus reactivated CMV on NK versus T cell maturation after HCT from different graft sources has not been defined. We compared the phenotype of NK and T cells from 292 recipients of allogeneic sibling (n = 118) or umbilical cord blood (UCB; n = 174) grafts based on recipient pretransplantation CMV serostatus and post-HCT CMV reactivation. This cohort was utilized to evaluate CMV-dependent increases in KIR-expressing NK cells exhibiting an adaptive phenotype (NKG2C(+)CD57(+)). Compared with CMV-seronegative recipients, those who reactivated CMV had the highest adaptive cell frequencies, whereas intermediate frequencies were observed in CMV-seropositive recipients harboring persistent/nonreplicating CMV. The same effect was observed in T cells and CD56(+) T cells. These adaptive lymphocyte subsets were increased in CMV-seropositive recipients of sibling but not UCB grafts and were correlated with lower rates of CMV reactivation (sibling 33% versus UCB 51%; P < .01). These data suggest that persistent/nonreplicating recipient CMV induces rapid production of adaptive NK and T cells from mature cells from sibling but not UCB grafts. These adaptive lymphocytes are associated with protection from CMV reactivation.
['Davis|Zachary B|ZB|', 'Cooley|Sarah A|SA|', 'Cichocki|Frank|F|', 'Felices|Martin|M|', 'Wangen|Rose|R|', 'Luo|Xianghua|X|', 'DeFor|Todd E|TE|', 'Bryceson|Yenan T|YT|', 'Diamond|Don J|DJ|', 'Brunstein|Claudio|C|', 'Blazar|Bruce R|BR|', 'Wagner|John E|JE|', 'Weisdorf|Daniel J|DJ|', 'Horowitz|Amir|A|', 'Guethlein|Lisbeth A|LA|', 'Parham|Peter|P|', 'Verneris|Michael R|MR|', 'Miller|Jeffrey S|JS|']
D064591:Allografts D036101:Cord Blood Stem Cell Transplantation D003587:Cytomegalovirus D003586:Cytomegalovirus Infections D005260:Female D018380:Hematopoietic Stem Cell Transplantation D006801:Humans D007694:Killer Cells, Natural D008297:Male D054340:Receptors, KIR D035781:Siblings D013601:T-Lymphocytes
Natural killer cells Cytomegalovirus reactivation Transplantation Clinical outcomes