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 (allo HCT) 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 allo HCT recipients from CMV-seronegative donors, with or without CMV reactivation. Results Nearly all of the CMV- CTLs during follow-up were CD45 RA− CCR7− effector memory/ CD45 RA+ 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 allo HCT 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 allo HCT. [ABSTRACT FROM AUTHOR]