Reconstitution of CMV pp65 and IE-1-specific IFN-[gamma] [CD8.sup.+] and [CD4.sup.+] T-cell responses affording protection from CMV DNAemia following allogeneic hematopoietic SCT

• Published in: Bone marrow transplantation (Basingstoke) Vol. 46; no. 11; p. 1437
• Main Authors: Tormo, N, Solano, C, Benet, I, Nieto, J, de la Camara, R, Lopez, J, Garcia-Noblejas, A, Munoz-Cobo, B, Costa, E, Clari, M.A, Hernandez-Boluda, J.C, Remigia, M.J, Navarro, D
• Format: Journal Article
• Language: English
• Published: Nature Publishing Group 01-11-2011
• Subjects: Antithymocyte globulin; Cellular immunity; Cytomegalovirus infections; Dosage and administration; Hematopoietic stem cells; Transplantation
• ISSN: 0268-3369
• DOI: 10.1038/bmt.2010.330

Threshold levels of CMV-specific T-cell populations presumably affording protection from active CMV infection in allo-SCT recipients have been proposed, but lack extensive validation. We quantified CMV pp65 and immediate-early 1-specific IFN-[gamma] [CD8.sup.+] and [CD4.sup.+] T cell responses at days +30, +60 and +90 after transplantation in 133 patients, and established cutoff cell levels protecting from CMV DNAemia within the first 120 days after transplantation. No patients showing IFN-[gamma] [CD8.sup.+] or IFN-[gamma] [CD4.sup.+] T-cell counts >1.0 and > 1.2cells/fiL, respectively, developed a subsequent episode of CMV DNAemia. Initial or recurrent episodes of CMV DNAemia occurred in the face of IFN-[gamma] T-cell levels below defined thresholds. Negative predictive values at day + 30 for the IFN-[gamma] [CD8.sup.+] and [CD4.sup.+] T-cell markers were 68.1 and 61.8%, respectively. Recipients of grafts from CMV seropositive, related or HLA-matched donors, or receiving non-myeloablative conditioning had nonsignificant tendencies to reach more frequently protective levels of both T-cell subsets at early and late (day + 365) times after transplantation. The use of antithymocyte globulin and umbilical cord blood transplantation were associated with impaired CMV-specific T-cell reconstitution. CMV-specific IFN-[gamma] [CD8.sup.+] and [CD4.sup.+] T-cell recovery occurred irrespective of detectable CMV DNAemia. Bone Marrow Transplantation (2011) 46, 1431-1443; doi: 10.1038/bmt.2010.330; published online 11 January 2011 Keywords: CMV; T-cell immunity; CMV DNAemia; IFN-[gamma]-producing T cells; pp65; immediate-early 1