title: 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.
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.
authors.affiliation: Department of Clinical and Tumor Immunology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands. gratama@immh.azr.nl
authors.forename: J W
authors.initials: JW
authors.lastname: Gratama
authors.forename: J W
authors.initials: JW
authors.lastname: van Esser
authors.forename: C H
authors.initials: CH
authors.lastname: Lamers
authors.forename: C
authors.initials: C
authors.lastname: Tournay
authors.forename: B
authors.initials: B
authors.lastname: Löwenberg
authors.forename: R L
authors.initials: RL
authors.lastname: Bolhuis
authors.forename: J J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D000998:Antiviral Agents / Q000627:therapeutic use; D019921:Biotinylation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology / Q000276:immunology; D018450:Disease Progression; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D015789:HLA-A2 Antigen / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000150:complications / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010750:Phosphoproteins / Q000737:chemistry / Q000276:immunology*; D012306:Risk; D012680:Sensitivity and Specificity; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000276:immunology*; D014766:Viremia / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D000998:Antiviral Agents; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D015774:Ganciclovir