title: Numbers of Foxp3-expressing CD4+CD25high T cells do not correlate with the establishment of long-term tolerance after allogeneic stem cell transplantation.
abstract: OBJECTIVE
  Regulatory CD4 T cells that express high levels of CD25 play a vital role in the maintenance of tolerance to self antigens and are required for the induction of nonresponsiveness to alloantigens. The long-term CD4+CD25high T-cell reconstitution after allogeneic stem cell transplantation is unknown. Here, we evaluated whether recovery of this T-cell subset might be linked to the establishment of full donor/recipient tolerance.
  
  
  METHODS
  The frequency of CD4+CD25high T cells was determined by Fluorescence Activated Cell Sorter (FACS) analysis in 31 patients, with a mean follow-up of more than 31 months posttransplant. The expression levels of Foxp3 mRNA were assessed by quantitative real-time polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Patients with or without graft-versus-host disease (GvHD) had significant and persistent CD4 T-cell lymphopenia. The relative frequency of CD25high cells and the expression levels of FoxP3 mRNA within this subset were similar between all patients and healthy controls. No significant difference was found in the number of Foxp3-expressing CD4+CD25high T cells in patients with or without GvHD. Finally, younger age and absence of previous GvHD were significantly linked to CD4+CD25high T-cell recovery.
  
  
  CONCLUSIONS
  The low number of Foxp3-expressing CD4+CD25high T cells in grafted patients is not a specific default of this compartment but a consequence of global CD4 T-cell lymphopenia after allogeneic stem cell transplantation. Moreover, levels of Foxp3 mRNA in the CD25+ T-cell compartment do not allow predicting the development of GvHD in the long term.
authors.affiliation: Unité INSERM U 728, Institut d'Hématologie, Hôpital Saint Louis, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Meignin
authors.forename: Régis
authors.initials: R
authors.lastname: Peffault de Latour
authors.forename: Julien
authors.initials: J
authors.lastname: Zuber
authors.forename: Armelle
authors.initials: A
authors.lastname: Régnault
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mounier
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lemaître
authors.forename: Hélène
authors.initials: H
authors.lastname: Dastot
authors.forename: Raphaël
authors.initials: R
authors.lastname: Itzykson
authors.forename: Agnès
authors.initials: A
authors.lastname: Devergie
authors.forename: Ana
authors.initials: A
authors.lastname: Cumano
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
authors.forename: Anne
authors.initials: A
authors.lastname: Janin
authors.forename: Antonio
authors.initials: A
authors.lastname: Bandeira
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors; D006086:Graft vs Host Disease / Q000276:immunology / Q000378:metabolism; D006402:Hematologic Diseases / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008231:Lymphopenia / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D020127:Recovery of Function / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2