Immune reconstitution of HLA-A*0201/BMLF1- and HLA-A*1101/LMP2-specific Epstein Barr virus cytotoxic T lymphocytes within 90 days after haploidentical hematopoietic stem cell transplantation

Abstract

Background

Haploidentical hematopoietic stem cell transplant (haplo-HSCT) recipients are at high risk for Epstein Barr virus (EBV)-related diseases. EBV-specific CD8⁺ cytotoxic T cells can control EBV-infected B cell expansion; however, no studies have investigated EBV-specific immune reconstitution after HSCT, particularly haplo-HSCT. Therefore, in this study, we aimed to characterize EBV-specific immune cell reconstitution after haplo-HSCT.

Methods

HLA-A*1101 and HLA-A*0201 pentamers folded with immunodominant EBV peptides were used to detect EBV-specific CD8⁺ T cells by flow cytometry in peripheral blood mononuclear cells from 19 haplo-HSCT recipients and the results were compared with those in controls. We also compared the EBV-specific pentamer-binding cell frequencies in patients with or without EBV-related diseases by flow cytometry.

Results

Pentamer-binding EBV-specific CD8⁺ T cells were detected at + 30, + 60 and + 90 days after haplo-HSCT in EBV-seropositive patients subjected to haplo-HSCT from an EBV-seropositive donor. The frequencies of the HLA-A*0201/BMLF1-GLC pentamer in haplo-HSCT patients at + 30 days were significantly lower than those in HLA-A*0201-positive healthy controls (p = 0.019) and patients at + 60 days (p = 0.003). The frequencies of the HLA-A*1101/LMP2-SSC pentamer at + 30, + 60, and + 90 days were significantly decreased compared with those in healthy controls (p = 0.009, 0.019, and 0.039, respectively); however, the frequencies of the HLA-A*1101/LMP2-SSC pentamer did not differ significantly among patients at + 30, + 60, and + 90 days (p = 0.886). There was a significant difference in the frequency of the HLA-A*0201/BMLF1-GLC pentamer at + 60 days between patients with and without EBV-related diseases (p = 0.024). Patients with EBV-related diseases showed lower percentages of HLA-A*0201/BMLF1-GLC specific CD8⁺ T cells.

Conclusions

Haplo-HSCT recipients could generate EBV-specific CD8⁺ T cells within + 30 days after transplantation. The HLA-A*0201/BMLF1-GLC pentamer cell frequency at + 60 days may be a useful indicator for monitoring EBV-related diseases in patients after haplo-HSCT. Transfusion with EBV-CTLs within 60 days after haplo-HSCT may have prophylactic effects against EBV-related diseases.