Objective This study aimed to investigate the association between early immune reconstitution and Epstein-Barr virus(EBV)reactivation by analyzing changes in natural killer(NK),B,and T cells and their functional status in the peripheral blood during the early post-transplant period.Methods This study included 23 patients who underwent haplo-hematopoietic stem cell transplantation(HSCT).The immune reconstitution ofNK cells,T cells,and B cells as well as the expression levels ofNK and T cell exhaustion markers(PD-1,TIM-3,and CTLA-4)and cytotoxic function at 1,2,and 3 months post-transplantation were compared between patients with EBV activation(EBV+group)and those without activation(EBV-group)post-transplantation.Results EBV activation occurred in nine patients post-transplantation(EBV+group),whereas 14 patients demonstrated no activation(EBV-group).All patients with EBV activation exhibited EBV viremia,and no EBV-associated diseases occurred.No significant differences in the clinical characteristics were found between the two groups of patients.The median proportion of CD3+CD8+T cells in the EBV+group was significantly lower than that in the EBV-group at 1 month post-transplantation(P=0.033).The median proportion of the CD3CD16negCD56bri subset in the EBV+group was significantly higher than that in the EBV-group at 2 months post-transplantation(P=0.046).No significant differences in the median proportions of CD3-CD19+B cells were observed between the two groups at 1,2,and 3 months post-transplantation.The expression of CTLA-4 on CD3-CD16briCD56dim NK cells in the EBV+group was significantly higher than that in the EBV-group at 1 month post-transplantation(P=0.033).The expression of TIM-3 on CD3+CD8+T cells in the EBV+group was significantly higher than that in the EBV-group(P=0.009).The expression level of TIM-3 on CD3-CD16negCD56dim NK cells in the EBV+group was significantly lower than that in the EBV-group at 2 months post-transplantation(P=0.023).The expression levels of TIM-3 on CD3+CD4+T cells in the EBV+group than those in the EBV-group at 1 and 3 months post-transplantation(P=0.002,P=0.043).The median positive rate of Granzyme B expression in CD3+CD8+T cells and CD3+CD4+T cells in the EBV+group was significantly lower than that in the EBV-group at 1-month post-transplantation(P=0.033,P=0.016).The median positive rate of Granzyme B expression in the CD3-CD16briCD56neg cell subset in the EBV+group was higher than that in the EBV-group at 2 months post-transplantation(P=0.012).The median positive rate of Granzyme B expression in CD3+CD4+T cells in the EBV+group remained significantly lower than that in the EBV-group at 2 months post-transplantation(P=0.049).The median positive rate of perforin expression in the CD3-CD16briCD56dim cell subset was significantly higher in the EBV+group than in the EBV-group at 3 months post-transplantation(P=0.003).The median positive rate of IFN-γ expression in CD3+CD8+T cells in the EBV+group was significantly lower than that in the EBV-group at 3 months post-transplantation(P=0.036).Conclusion Delayed NK cell and T lymphocyte reconstitution,high exhaustion marker expression,and weakened cytotoxic functions may be related to EBV reactivation after haploidentical HSCT.
Allogeneic hematopoietic stem cell transplantationEpstein-barr virusImmune reconstitutionExhaustion markersImmune function
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