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Blood, 1 March 2001, Vol. 97, No. 5, pp. 1232-1240
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Direct visualization of cytomegalovirus-specific T-cell
reconstitution after allogeneic stem cell transplantation
Kate Cwynarski,
Jenni Ainsworth,
Mark Cobbold,
Simon Wagner,
Prem Mahendra,
Jane Apperley,
John Goldman,
Charles Craddock, and
Paul A. H. Moss
From the CRC Institute for Cancer Studies, University
of Birmingham, Edgbaston, United Kingdom; the Department of Hematology,
University Hospital, Birmingham; and the Department of Hematology,
Hammersmith Hospital, ICSM, London, United Kingdom.
Cytomegalovirus (CMV) remains an important cause of morbidity and
mortality after allogeneic stem cell transplantation (SCT), but
cytotoxic T lymphocytes (CTL) may play a critical role in controlling
CMV reactivation. Fluorescent HLA-peptide tetramers containing
immunodominant peptides from CMV were used to prospectively monitor the recovery of CMV CTL in recipients of allogeneic transplants from siblings (n = 13) or unrelated donors (n = 11). In patients given allografts from a sibling when both the patient and donor were
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-specific immunity was not observed if either the
donor or recipient was seronegative for CMV. In recipients of
transplants from volunteer unrelated donors, recovery of CMV-specific
CTL was delayed in comparison to that in recipients of transplants from
siblings and no CTL were observed within the first 100 days after SCT.
CTL numbers were increased after episodes of CMV reactivation but were
suppressed by prednisolone therapy. Recovery of CMV-specific CTL to
levels greater than 10 × 106/L was associated with
protection from CMV disease. It was concluded that use of HLA-peptide
tetramers to quantify CMV CTL is valuable for studying T-cell responses
after allogeneic SCT. It should allow prediction of CMV reactivation in
individual patients and assist in the development of adoptive T-cell immunotherapy.

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