title: Appearance of cytomegalovirus-specific T-cells predicts fast resolution of viremia post hematopoietic stem cell transplantation.
abstract: Cytomegalovirus (CMV) specific T-cells are known to provide long-term control of CMV reactivation, which is a frequent complication of hematopoietic stem cell transplantation. We have studied 58 pediatric patients after hematopoietic stem cell transplantation who suffered from CMV reactivation to reveal which functional T cell subset is best correlating with successful reactivation resolution and which protects from reactivation episode.
  
  
  
  Detection of 30 combinatorial subsets of four types of response to ex vivo CMV stimulation (IFNγ secretion, IL-2 secretion, CD40L upregulation and degranulation) that were detectable on either CD8+ or CD4+ T cells through flow cytometry intracellular cytokine staining was used.
  
  
  
  We found that the presence of CD8+ dual positive (IFNγ+ and IL-2+) cells is the most accurate functional parameter that can predict fast resolution of CMV reactivation. Next, we show that the presence of CD8+ dual positive (IFNγ+ and IL-2+) and CD8+ IFNγ+ cells provides a protective effect (a hazard risk of 0.28 (confidence interval 0.18 - 0.43) and 0.45 (CI 0.27 - 0.75), respectively) and the presence of corticotherapy increases the risk of reactivation (HR 2.47 (CI 1.82-3.36)). Thus, a patient without corticotherapy and with both of the critical T cell subsets present has a cumulative 19.6 times lower risk of developing CMV reactivation than a patient on corticotherapy and without CD8+ dual positive (IFNγ+ and IL-2+) or CD8+ IFNγ+ cells.
  
  
  
  We have established parameters of CMV specific functional response ex vivo that can be used in assisting clinical management of patients with CMV reactivation. © 2015 International Clinical Cytometry Society.
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.|CLIP-Childhood Leukemia Investigation Prague, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Pelák
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.|CLIP-Childhood Leukemia Investigation Prague, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Stuchlý
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.|CLIP-Childhood Leukemia Investigation Prague, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Król
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Hubáček
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Keslová
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Sedláček
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Formánková
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Starý
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.|CLIP-Childhood Leukemia Investigation Prague, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Hrušák
authors.affiliation: Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.|CLIP-Childhood Leukemia Investigation Prague, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, V Uvalu 84, Prague, 150 06, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Kalina
mesh_terms: D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000821:virology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007223:Infant; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014766:Viremia / Q000378:metabolism*; D055815:Young Adult
keywords: T-cells; bone marrow transplantation; cytomegalovirus; flow cytometry; immune reconstitution