Persistence of recipient-derived as well as donor-derived clones of cytomegalovirus pp65-specific cytotoxic T cells long after allogeneic hematopoietic stem cell transplantation

Background: Cytomegalovirus (CMV)-specific CD8⁺ cytotoxic T lymphocytes (CMV-CTLs) play a crucial role in preventing CMV disease. However, the actual in vivo dynamics of CMV-CTL clones after allogeneic hematopoietic stem cell transplantation (alloHCT) are still unclear. Methods: Using a single-cell T-cell receptor repertoire analysis, we monitored clones and chimerism of CMV-CTLs in 3 CMV-seropositive alloHCT recipients from CMV-seronegative donors, with or without CMV reactivation. Results: Nearly all of the CMV-CTLs during follow-up were CD45RA^-CCR7^- effector memory/CD45RA⁺CCR7^- effector T cells, and were highly matured. In each case, the use of BV gene families was restricted, especially in BV5, 7, 28, and 29. Although no common predominant CMV-CTL clones were found, several shared motifs of complementarity-determining region-3 were identified among the 3 cases; QGA in all, TGE and TDT in Case 1 and Case 2, and RDRG in Case 2 and Case 3. In all cases, CMV-CTL clones that were detected for the first time after alloHCT persisted as the dominant clones. In Case 1, without CMV reactivation, recipient-derived CMV-CTLs exclusively persisted as a dominant clone, while all CMV-CTLs in the other 2 cases, with CMV reactivation, were donor derived. Conclusion: Clone monitoring and chimerism analyses should help to further clarify novel aspects of immuno-reconstitution after alloHCT.