Early reconstitution of effector memory CD4+CMV-specific T cells protects against CMV reactivation following allogeneic SCT

Reactivation of CMV is a common complication following allogeneic haematopoietic SCT and is associated with signi. cant morbidity and mortality. The relative importance of the CD4+ and CD8+ components of the CMVspecific immune response in protection from reactivation is unclear. The CMV-specific CD4+ and CD8+ immune response was measured at serial time points in 32 patients following allogeneic HSCT. Intracellular cytokine staining following CMV lysate stimulation and HLA-peptide tetramers were used to determine CMV-specific CD4+ and CD8+ responses, respectively. A deficient CMV-specific CD4+ T-cell immune response within the first 30-50 days post transplant was associated with high risk of viral reactivation. Patients with combined impairment of the CD4+ and CD8+ immune response within the first 100 days were susceptible to late viral reactivation. The frequency of CMV-specific CD4+ T cells correlated with CMV-specific CD8+ T cells, comprising 10% of the whole T-cell repertoire. Early CMV-specific CD4+ T-cell reconstitution was dominated by effector memory cells with normal levels of IL-2 resuming 6 months following trans plantation. In summary, both CD4 and CD8 CMV-specific immune reconstitution is required for protection from recurrent activation. Measurement of the magnitude of the CMV-specific CD4+ immune response is useful in managing viral reactivation following HSCT. Bone Marrow Transplantation (2009) 43, 853-861; doi: 10.1038/bmt.2008.403; published online 22December 2008