Circulating NKG2C + NK cell expressing CD107a/LAMP-1 subsets at the onset of CMV reactivation in seropositive kidney transplant recipients

Abstract

Cytomegalovirus (CMV) infection contributes to morbidity and mortality among kidney transplant recipients. Natural killer (NK) cells can battle against CMV in kidney transplant recipients (KTRs). This study aimed to analyze the association between CMV reactivation and the proportion of NK cell subsets and their activity. In a cross-sectional study, ten CMV reactivated KTRs, and ten non- CMV reactivated ones were recruited. Ten matched healthy controls were also included in this cohort. The presence of anti-CMV-IgG Ab in both KTR subgroups from seronegative donors and healthy controls was determined. The frequency of distinct subsets of memory-like NK cells was analyzed through NKG2C, NKG2A, and CD57 using flow cytometry. The activity of NK cells was evaluated after stimulation via coculture with K562 cell line and then assessment of the frequency of CD107a and granzyme B. The mRNA levels of transcription factors, including T-bet, EAT, and inflammatory proteins, including IFN-γ and perforin contributing to NK cell activation, were also evaluated.Results showed a significantly lower frequency of NKG2C + NKG2A-CD57+ NK cell population in CMV-reactivated KTRs compared to non-reactivated ones (P-value:0.003). NKG2C+ NK cells expressing CD107a/LAMP-1 significantly was increased in CMV-reactivated KTRs compared to non-reactivated ones (P-value: 0.0002). The mRNA level of IFN-γ had a significant increase in the CMV-reactivated KTRs vs. nonreactive ones (P-value: 0.004). Finally, evaluation of the NK cells' cytotoxicity and activity through assessment of CD107a/LAMP-1 expression and IFN-γ secretion may be helpful for the identification of the risk of CMV reactivation in KTRs.