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Blood, 1 September 2001, Vol. 98, No. 5, pp. 1358-1364
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Tetramer-based quantification of cytomegalovirus (CMV)-specific
CD8+ T lymphocytes in T-cell-depleted stem cell
grafts and after transplantation may identify patients at risk for
progressive CMV infection
Jan W. Gratama,
Joost W. J. van Esser,
Cor H. J. Lamers,
Claire Tournay,
Bob Löwenberg,
Reinder L. H. Bolhuis, and
Jan J. Cornelissen
From the Departments of Clinical and Tumor Immunology
and of Hematology, Erasmus Medical Center Rotterdam, Rotterdam, the
Netherlands; and Immunotech SA, Marseille, France.
Recovery of cytomegalovirus (CMV)-specific T-cell-mediated
immunity after allogeneic hematopoietic stem cell transplantation (SCT)
is critical for protection against CMV disease. The study used
fluorochrome-conjugated tetrameric complexes of HLA-A2 molecules loaded
with the immunodominant NLVPMVATV (NLV) peptide derived from the CMV
protein pp65 to quantify A2-NLV-specific CD8+ T cells in
partially T-cell-depleted grafts administered to 27 HLA-A*0201+ patients and to monitor recovery of these T
cells during the first 12 months after SCT. None of the 9 CMV-seronegative patients became infected with CMV, whereas 14 of 18 CMV-seropositive patients developed CMV antigenemia after SCT.
CMV-seropositive recipients of grafts from CMV-seronegative donors
required more preemptive treatment with ganciclovir (GCV) than those of
grafts from CMV-seropositive donors (3 [1-6] versus 1 [0-3]
courses, respectively; P = .009). The number of
A2-NLV-specific CD8+ T cells in the grafts correlated
inversely with the number of preemptive GCV courses administered
(r =  0.61; P = .01). None of the 9 CMV-seronegative patients mounted a CMV-specific immune response as
measured by monitoring A2-NLV-specific CD8+ T cells after
SCT. Thirteen of 14 CMV-seropositive patients without CMV disease
recovered these T cells. In spite of preemptive GCV treatment, CMV
disease developed in 4 patients, who all failed to recover
A2-NLV-specific CD8+ T cells after SCT
(P = .002). Thus, enumeration of HLA-restricted, CMV-specific CD8+ T cells in the grafts and monitoring of
these T cells after SCT may constitute a rapid and sensitive tool to
identify SCT recipients at risk for developing CMV disease.
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