Kinetics of cytomegalovirus (CMV) pp65 and IE-1-specific IFNγ CD8⁺ and CD4⁺ T cells during episodes of viral DNAemia in allogeneic stem cell transplant recipients: Potential implications for the management of active CMV infection

The dynamics of CMV pp65 and IE-1-specific IFNγ-producing CD8⁺ (IFNγ CD8⁺) and CD4⁺ (IFNγ CD4⁺) T cells and CMV DNAemia were assessed in 19 pre-emptively treated episodes of active CMV infection. Peripheral counts of IFNγ CD8⁺ and IFNγ CD4⁺ T cells inversely correlated with CMV DNAemia levels (P = <0.001 and P = 0.003, respectively). A threshold value of 1.3 cells/µl predicting CMV DNAemia clearance was established for IFNγ CD8⁺ T cells (PPV, 100%; NPV, 93%) and for IFNγ CD4⁺ T cells (PPV, 100%; NPV, 75%). Undetectable T-cell responses were usually observed at the time of initiation of pre-emptive therapy. Either a rapid (within 7 days) or a delayed (median 31 days) expansion of both T-cell populations concomitant with CMV DNAemia clearance was observed in 5 and 8 episodes, respectively. An inconsistent or a lack of expansion of both T-cell subsets was related to a persistent CMV DNAemia. Robust and maintained CMV-specific T-cell responses after CMV DNAemia clearance and cessation of antiviral therapy were associated with a null incidence of relapsing infections at least during the following month. Data obtained in the present study may be helpful in the design of therapeutic strategies for the management of active CMV infections in the allo-SCT recipient. J. Med. Virol. 82: 1208–1215, 2010. © 2010 Wiley-Liss, Inc.