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Early cytomegalovirus reactivation leaves a specific and dynamic imprint on the reconstituting T cell compartment long-term after hematopoietic stem cell transplantation.
Biol Blood Marrow Transplant. 2014 May; 20(5):655-61.BB

Abstract

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.

Authors+Show Affiliations

Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: g.lugthart@lumc.nl.Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands.Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands.Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands.Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands; Pediatric HSCT unit, Leiden University Medical Center, Leiden, The Netherlands.Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands.Department of Pediatrics, Laboratory for Immunology, Leiden University Medical Center, Leiden, The Netherlands; Pediatric HSCT unit, Leiden University Medical Center, Leiden, The Netherlands.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24462981

Citation

Lugthart, Gertjan, et al. "Early Cytomegalovirus Reactivation Leaves a Specific and Dynamic Imprint On the Reconstituting T Cell Compartment Long-term After Hematopoietic Stem Cell Transplantation." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 20, no. 5, 2014, pp. 655-61.
Lugthart G, van Ostaijen-Ten Dam MM, Jol-van der Zijde CM, et al. Early cytomegalovirus reactivation leaves a specific and dynamic imprint on the reconstituting T cell compartment long-term after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(5):655-61.
Lugthart, G., van Ostaijen-Ten Dam, M. M., Jol-van der Zijde, C. M., van Holten, T. C., Kester, M. G., Heemskerk, M. H., Bredius, R. G., van Tol, M. J., & Lankester, A. C. (2014). Early cytomegalovirus reactivation leaves a specific and dynamic imprint on the reconstituting T cell compartment long-term after hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 20(5), 655-61. https://doi.org/10.1016/j.bbmt.2014.01.018
Lugthart G, et al. Early Cytomegalovirus Reactivation Leaves a Specific and Dynamic Imprint On the Reconstituting T Cell Compartment Long-term After Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2014;20(5):655-61. PubMed PMID: 24462981.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Early cytomegalovirus reactivation leaves a specific and dynamic imprint on the reconstituting T cell compartment long-term after hematopoietic stem cell transplantation. AU - Lugthart,Gertjan, AU - van Ostaijen-Ten Dam,Monique M, AU - Jol-van der Zijde,Cornelia M, AU - van Holten,Tessa C, AU - Kester,Michel G D, AU - Heemskerk,Mirjam H M, AU - Bredius,Robbert G M, AU - van Tol,Maarten J D, AU - Lankester,Arjan C, Y1 - 2014/01/23/ PY - 2013/12/05/received PY - 2014/01/17/accepted PY - 2014/1/28/entrez PY - 2014/1/28/pubmed PY - 2014/12/15/medline KW - Cytomegalovirus KW - Immune reconstitution KW - Pediatric hematopoietic stem cell transplantation KW - T cell differentiation SP - 655 EP - 61 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 20 IS - 5 N2 - 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. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/24462981/Early_cytomegalovirus_reactivation_leaves_a_specific_and_dynamic_imprint_on_the_reconstituting_T_cell_compartment_long_term_after_hematopoietic_stem_cell_transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(14)00049-4 DB - PRIME DP - Unbound Medicine ER -