title: Cytomegalovirus-specific CD4+ and CD8+ T-cells follow a similar reconstitution pattern after allogeneic stem cell transplantation.
abstract: Cytomegalovirus (CMV) is a common herpes virus that can cause significant morbidity and mortality in immunocompromised individuals, particularly those undergoing allogeneic stem cell transplantation (SCT) for hematological malignancies. Recent studies have examined the kinetics of CMV-specific CD8+ T-cell reconstitution after SCT transplantation and have found virus-specific cytotoxic T-lymphocyte regeneration to be dependent on CMV serologic status and CMV reactivation events. However, the reconstitution kinetics of CMV-specific CD4+ T-cells under these same circumstances were not addressed. In this study, we used HLA class I peptide tetramer for CMV pp65 and cytokine flow cytometry to follow the reconstitution of both CD4+ and CD8+ CMV-specific T-cells after allogeneic SCT. We found that following SCT in which both donors and recipients are CMV seropositive, virus-specific CD4+ T-helper cells show the same reconstitution kinetics as CD8+ cytotoxic T-cells. Following CMV reactivation, a synchronous but temporary increase in both CD4+ and CD8+ CMV-specific lymphocytes occurs. The pattern repeats itself after subsequent episodes of CMV reactivation. These data imply that both CD4+ and CD8+ lymphocytes are necessary for an efficient immune response to CMV and suggest that CD4+ and CD8+ CMV-specific T-cells are required for the complete restoration of CMV immunity. These findings may have important implications in the development of CMV-specific adoptive immunotherapy strategies.
authors.affiliation: Westmead Institute for Cancer Research, Westmead Millennium Institute, University of Sydney, New South Wales, Australia.
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Foster
authors.forename: David J
authors.initials: DJ
authors.lastname: Gottlieb
authors.forename: Mary
authors.initials: M
authors.lastname: Sartor
authors.forename: Mark S
authors.initials: MS
authors.lastname: Hertzberg
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bradstock
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D003587:Cytomegalovirus / Q000254:growth & development / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000139:chemically induced / Q000175:diagnosis / Q000276:immunology; D005260:Female; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000254:growth & development; D007700:Kinetics; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D036102:Peripheral Blood Stem Cell Transplantation; D010750:Phosphoproteins / Q000276:immunology; D014184:Transplantation, Homologous; D014763:Viral Matrix Proteins / Q000276:immunology; D014775:Virus Activation / Q000276:immunology
chemical_list: D010446:Peptide Fragments; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa