title: 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.
abstract: 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-gamma-producing CD4+ and CD8+ T cells upon in vitro activation using peptide pools representing the CMV pp65 and IE-1 proteins were assessed at multiple 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.
authors.affiliation: Department of Internal Oncology, Erasmus MC, Rotterdam, The Netherlands. j.w.gratama@erasmusmc.nl
authors.forename: Jan W
authors.initials: JW
authors.lastname: Gratama
authors.forename: Rik A
authors.initials: RA
authors.lastname: Brooimans
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Kees
authors.initials: K
authors.lastname: Sintnicolaas
authors.forename: Gerard
authors.initials: G
authors.lastname: van Doornum
authors.forename: Hubertus G
authors.initials: HG
authors.lastname: Niesters
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology*; D012008:Recurrence; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D014763:Viral Matrix Proteins / Q000276:immunology*; D014775:Virus Activation; D017735:Virus Latency
chemical_list: C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D007166:Immunosuppressive Agents; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma