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.
Bibliographical noteFunding Information:
Financial disclosure: This work was supported by National Cancer Institute and National Institutes of Health ( P01 CA111412 [J.S.M., D.J.W., M.R.V., S.C., and T.E.D.], CA65493 [J.S.M., T.E.D., S.C., B.R.B., J.W., and M.R.V.], R01 CA077544 , R01 AI103960 , R01 AI63356 [D.J.D.], R01 AI100879 [M.R.V.], R01 CA72669 [B.R.B.] and T32 HD007062 ).
© 2015 American Society for Blood and Marrow Transplantation.
- Clinical outcomes
- Cytomegalovirus reactivation
- Natural killer cells