Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation

Cytomegalovirus (CMV) remains an important cause of morbidity and mortality after allogeneic stem cell transplantation (SCT), but cytotoxic T lymphocy tes (CTL) may play a critical role in controlling CMV reactivation. Fluores cent HLA-peptide tetramers containing immunodominant peptides from CMV were used to prospectively monitor the recovery of CMV CTL in recipients of all ogeneic transplants from siblings (n = 13) or unrelated donors (n = 11). In patients given allografts from a sibling when both the patient and donor w ere seropositive for CMV before SCT, recovery of CMV-specific CTL was rapid and reached up to 21% of all CD8(+) T cells. Early reconstitution of CMV-s pecific immunity was not observed if either the donor or recipient was sero negative for CMV. In recipients of transplants from volunteer unrelated don ors, recovery of CMV-specific CTL was delayed in comparison to that in reci pients of transplants from siblings and no CTL were observed within the fir st 100 days after SCT. CTL numbers were increased after episodes of CMV rea ctivation but were suppressed by prednisolone therapy. Recovery of CMV-spec ific CTL to levels greater than 10 x 10(6)/L was associated with protection from CMV disease. It was concluded that use of HLA-peptide tetramers to qu antify CMV CLL is valuable for studying T-cell responses after allogeneic S CT. It should allow prediction of CMV reactivation in individual patients a nd assist in the development of adoptive T-cell immunotherapy. (Blood. 2001 ;97:1232-1240) (C) 2001 by The American Society of Hematology.