Early cytomegalovirus reactivation leaves a specific and dynamic imprint on the reconstituting T cell compartment long-term after hematopoietic stem cell transplantation.
Human cytomegalovirus (CMV) reactivation frequently occurs during the early phase of immune recovery after allogeneic hematopoietic stem cell transplantation (HSCT). Whereas the recovery of virus-specific immunity in the early phase after HSCT is extensively studied, the impact of CMV on the reconstitution and composition of the T cell compartment long-term after HSCT is unknown. We analyzed T cell reconstitution 1 to 2 years after HSCT in 131 pediatric patients. One year after HSCT, patients with early CMV reactivation (n = 46) had 3-fold higher CD8(+) T cell numbers (median, 1323 versus 424 cells/μL; P < .0001) compared with patients without CMV reactivation (n = 85). This effect, caused by a major expansion of CD8(+) effector memory (EM) and end-stage effector (EMRA) T cells, was independent of pretransplantation donor and recipient CMV serostatus and not seen after Epstein-Barr virus or adenovirus reactivations. At 1 and 2 years after HSCT, the absolute numbers of CD8(+) naive and central memory T cells, as well as CD4(+) naive, CM, EM, and EMRA T cells, did not differ between patients with or without CMV reactivation. In the second year after HSCT, a significant contraction of the initially expanded CD8(+) EM and EMRA T cell compartments was observed in patients with early CMV reactivation. In conclusion, CMV reactivation early after pediatric HSCT leaves a specific and dynamic imprint on the size and composition of the CD8(+) T cell compartment without compromising the reconstitution of CD8(+) and CD4(+) naive and central memory T cells pivotal in the response to neo and recall antigens.
Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: g.lugthart@lumc.nl.
Gertjan
G
Lugthart
Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands.
Monique M
MM
van Ostaijen-Ten Dam
Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands.
Cornelia M
CM
Jol-van der Zijde
Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands.
Tessa C
TC
van Holten
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Michel G D
MG
Kester
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Mirjam H M
MH
Heemskerk
Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands; Pediatric HSCT unit, Leiden University Medical Center, Leiden, The Netherlands.
Robbert G M
RG
Bredius
Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands.
Maarten J D
MJ
van Tol
Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands; Pediatric HSCT unit, Leiden University Medical Center, Leiden, The Netherlands.
Arjan C
AC
Lankester
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology / Q000628:therapy / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology / Q000628:therapy / Q000821:virology; D005260:Female; D006402:Hematologic Diseases / Q000150:complications / Q000276:immunology / Q000628:therapy / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007156:Immunologic Memory; D007223:Infant; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D008297:Male; D013997:Time Factors; D014184:Transplantation, Homologous; D014775:Virus Activation
Cytomegalovirus; Immune reconstitution; Pediatric hematopoietic stem cell transplantation; T cell differentiation