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

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-γ CD8+ and CD4 + 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-γ CD8+ or IFN-γ CD4+ T-cell counts > 1.0 and > 1.2 cells/μL, respectively, developed a subsequent episode of CMV DNAemia. Initial or recurrent episodes of CMV DNAemia occurred in the face of IFN-γ T-cell levels below defined thresholds. Negative predictive values at day +30 for the IFN-γ CD8+ and CD4+ 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 anti-thymocyte globulin and umbilical cord blood transplantation were associated with impaired CMV-specific T-cell reconstitution. CMV-specific IFN-γ CD8+ and CD4+ T-cell recovery occurred irrespective of detectable CMV DNAemia.