Rapid reconstitution of Epstein-Barr virus-specific T lymphocytes following allogeneic stem cell transplantation

Epstein-Barr virus (EBV)-specific CD8 T lymphocytes are present at remarkab ly high frequencies in healthy EBV+ individuals and provide protection from EBV-associated lymphoproliferative diseases. Allogeneic peripheral blood s tem cell transplantation (allo-PBSCT) is a commonly used therapy in which T -cell surveillance for EBV is temporarily disrupted. Herein, human leukocyt e antigen (HLA) class I tetramers were used to investigate the reestablishm ent of the EBV-specific CD8 T-cell repertoire in patients following allo-PB SCT. CD8(+) T cells specific for lytic and latent cycle-derived EBV peptide s rapidly repopulate the periphery of matched sibling allo-PBSCT patients. The relative frequencies of T cells specific for different EBV peptides in transplantation recipients closely reflect those of their respective donors . Investigation of patients at monthly intervals following unmanipulated al lo-PBSCT demonstrated that the frequency of EBV-specific T cells correlates with the number of EBV genome copies in the peripheral blood and that expa nsion of EBV-specific T-cell populations occurs even in the setting of immu nosuppressive therapy. In contrast, patients undergoing T-cell-depleted or unrelated cord blood transplantation have undetectable EBV-specific T cells , even in the presence of Epstein-Barr viremia. The protective shield provi ded by EBV-specific CD8 T cells is rapidly established following unmanipula ted matched sibling allo-PBSCT and demonstrates that HLA class I tetramers complexed with viral peptides can provide direct and rapid assessment of pa thogen-specific immunity in this and other vulnerable patient populations. (Blood. 2000;96:2814-2821) (C) 2000 by The American Society of Hematology.