Monitoring cytomegalovirus IE-1 and PP65-specific CD4+ and CD8+ T-cell responses after allogeneic stem cell transplantation may identify patients at risk for recurrent CMV reactivations
We studied the recovery of CMV-specific CD4+and CD8+T-cell immunity in 52 recipients of allogeneic stem cell transplantation (SCT). The proportions of IFN-γ-producing CD4+and CD8+T cells upon in vitro activation using peptide pools representing the CMV pp65 and IE-1 proteins were assessed at multi-ple time points post SCT, and correlated with the occurrence of CMV reactivation. In a retrospective analysis, recurrent CMV reactivations occurred in 9 patients and were associated with low pp65-specific CD4+T-cell and low IE-1-specific CD8+T-cell reactivities, whereas patients without detectable CMV reactivation (n = 30) or a single reactivation (n = 13) showed a better recovery of these immune responses. CD4+T-cell responses to IE-1 were infrequent in most patients, whereas CD8+T-cell responses to pp65 occurred frequently, but did not correlate with protection against (recurrent) reactivation. Prospectively, CMV-specific T-cell responses could be studied prior to 14 reactivation episodes in 8 patients. CD4+T-cell responses to IE-1 and pp65 were positive in only 1 and 2 episodes, respectively. CD8+T-cell responses against IE-1 were positive in 4, but against pp65 in 12 episodes, again showing that CD8+T-cell reactivity against pp65 did not prevent CMV reactivation. Thus, monitoring of particular CMV-specific CD4+and CD8+T-cell responses after allogeneic SCT may identify patients at risk for recurrent CMV reactivations.