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 of NK cells, T cells, and B cells as well as the expression levels of NK 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 CD3 -CD16 negCD56 bri 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 -CD16 briCD56 dim 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 -CD16 negCD56 dim 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 -CD16 briCD56 neg 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 -CD16 briCD56 dim 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.

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 of NK cells, T cells, and B cells as well as the expression levels of NK 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 CD3 -CD16 negCD56 bri 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 -CD16 briCD56 dim 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 -CD16 negCD56 dim 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 -CD16 briCD56 neg 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 -CD16 briCD56 dim 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.

BACKGROUND:Recently,acellular dermal matrix allograft has been widely used in the repair of oral mucosal defects.But little information is about the heterogeneous acellular dermal matrix (HADM) patch for repair of oral mucosal defects.OBJECTIVE:To investigate the efficacy and biosafety of HADM in the repair of oral mucosal defects.METHODS:In total 71 patients with oral benign or malignant tumors who had oral mucosal or soft tissue defects following tumorectomy were included in this study.These patients comprised 37 males and 34 females,and were averaged 45 years (range,20-70 years old).Of them,42 suffered from benign tumors and 29 from malignant tumors.HADM patches were used for repair of oral mucosal defects.The survival,color,and texture of HADM patches were observed.Shrinkage rate of HADM patches was compared between regions without supports from hard tissues (cheeks,tongue,and mouth floor) and with supports from hard tissues (gingiva,hard palate).RESULTS AND CONCLUSION:All 71 HADM completely survived.No necrosis and infection occurred.At 2 weeks after transplantation,(98.20±5.20) % of patch area survived.At 3 months after transplantation,patches showed similar color to surrounding oral mucosa and most patients had sense of tension to different extents.At 6 months after transplantation,cell creeping substitution and vasculadzation were successfully accomplished in the region of patch transplantation.Patches grew stably,with smooth pink appearance and good elasticity,and no further shdnkage.Patients felt normal.HADM patch shrank primarily at 2 weeks-1 month after transplantation,and tended to be stable at 3 months.There was no significant difference in tissue morphology between surgical region and normal tissue.The HADM shdnkage rate was significantly higher in regions without supports from hard tissues than regions with supports from hard tissues.These findings indicate that HADM patches have advantages in repair of oral mucosal defects including good histocompatibility,wide source,simple manipulation,and able to cover the wound surface in the early state,promote wound surface healing,and reduce scar formation,and can be used as an ideal matedal for repair of oral mucosal defects.