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

Recovery of cytomegalovirus (CMV)specific T-cell-mediated Immunity after al logeneic hematopoietic stem cell transplantation (SCT) is critical for prot ection against CMV disease. The study used fluorochrome-conjugated tetramer ic complexes of HLA-A2 molecules loaded with the immunodominant NLVPMVATV ( NLV) peptide derived from the CMV protein pp65 to quantity 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 infect ed with CMV, whereas 14 of 18 CMV-seropositive patients developed CMV antig enemia after SCT. CMV-seropositive recipients of grafts from CMV-seronegati ve donors required more preemptive treatment with ganciclovir (GCV) than th ose 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 t he grafts correlated inversely with the number of preemptive GCV courses ad ministered (r = -0.61; P = .01). None of the 9 CMV-seronegative patients mo unted a CMV-specific immune response as measured by monitoring A2-NLV-speci fic CD8(+) T cells after SCT. Thirteen of 14 CMV-seropositive patients with out CMV disease recovered these T cells. In spite of preemptive GCV treatme nt, CMV disease developed in 4 patients, who all failed to recover A2-NLV-s pecific CD8(+) T cells after SCT (P = .002). Thus, enumeration of HLA-restr icted, 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 r ecipients at risk for developing CMV disease. (C) 2001 by The American Soci ety of Hematology.