Cytomegalovirus (CMV) reactivation has an impact on significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are the first donor reconstituted lymphocytes after HSCT and play a key role in virus infection. However, the function and reconstitution of NK cells in HSCT remain elusive. We performed a thorough and sequential analysis of NK functions in patients who received HSCT from CMV-seropositive donors, and investigated the association between the NK reconstitution and CMV reactivation.

Method: We monitored NK cytotoxicity, NK activity for cytokine production and NK phenotype expression in 38 patients at different time (0, 30, 60, 90, 120, and 150 days) after HSCT. The NK activity for proinflammatory cytokine production (IFN-γ) was assessed using NKvue kit. NK activity was represented by IFN-γ levels after stimulation of NK cells. CMV viremia (>1000 copies/ml) was monitored at the same time by quantitative PCR.

Results: Patients who experienced CMV viremia tend to keep decreased NK functions compared to patients without CMV viremia, and there was significant difference at post-HSCT 60 days (K562 cytolysis, 8.9% vs. 52.2, P=0.047; ADCC, 11.9% vs. 40.1%, P=0.011). The frequencies of NK cells, especially CD56bright NK cells remained higher in patients experiencing CMV viremia versus those in patients without CMV viremia, and showed significance at 30 days later HSCT (p=0.014). However, CD3+ T cells and NKT (CD3+CD56+) cells were significantly decreased in patients with CMV viremia (p=0.003). Maturation of NK cells presenting the loss of NKG2A expression was associated with CMV reactivation (p=0.047). In terms of NK activity, the IFN-γ producing activities showed weak correlation with NK K562 cytotoxicity (r=0.326, p<0.0001) and ADCC (r=0.194, p=0.033), but IFN-γ productions were not significantly associated with CMV reactivation.

Conclusion: In this study, CMV reactivation after HSCT was associated with a decreased NK function and increased frequency of CD56bright NK cell population. The close monitoring of NK reconstitution might predict the clinical outcome following HSCT.

CITATION INFORMATION: Ki Hyun P, Hyeyoung L, Ji Hyeong R, Yonggoo K, Kyungja H, Byung Sik C, Hee-Je K, Woosung M, Eun-Jee O. Sequential Monitoring of Natural Killer Cell Reconstitution Against CMV Reactivation After Allogeneic Hematopoietic Stem Cell Transplantation. Am J Transplant. 2017;17 (suppl 3).

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