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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.
- Source :
-
Blood [Blood] 2001 Sep 01; Vol. 98 (5), pp. 1358-64. - Publication Year :
- 2001
-
Abstract
- 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.
- Subjects :
- Adolescent
Adult
Antibodies, Viral immunology
Antiviral Agents therapeutic use
Biotinylation
Cytomegalovirus Infections diagnosis
Cytomegalovirus Infections drug therapy
Cytomegalovirus Infections etiology
Cytomegalovirus Infections immunology
Disease Progression
Female
Ganciclovir therapeutic use
HLA-A2 Antigen immunology
Humans
Immunity, Cellular
Immunologic Deficiency Syndromes complications
Immunologic Deficiency Syndromes immunology
Male
Middle Aged
Peptide Fragments chemistry
Peptide Fragments immunology
Phosphoproteins chemistry
Risk
Sensitivity and Specificity
Viral Matrix Proteins chemistry
Viremia diagnosis
Viremia drug therapy
Viremia epidemiology
Viremia etiology
Viremia immunology
Antigens, Viral immunology
CD8-Positive T-Lymphocytes immunology
Cytomegalovirus immunology
Cytomegalovirus Infections epidemiology
Hematopoietic Stem Cell Transplantation adverse effects
Hematopoietic Stem Cell Transplantation methods
Immunodominant Epitopes immunology
Phosphoproteins immunology
Viral Matrix Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 98
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 11520783
- Full Text :
- https://doi.org/10.1182/blood.v98.5.1358