Numbers of Foxp3-expressing CD4+CD25high T cells do not correlate with the establishment of long-term tolerance after allogeneic stem cell transplantation.
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.
Meignin
Véronique
V
Unité INSERM U 728, Institut d'Hématologie, Hôpital Saint Louis, Paris, France.
Peffault de Latour
Régis
R
Zuber
Julien
J
Régnault
Armelle
A
Mounier
Nicolas
N
Lemaître
Fabrice
F
Dastot
Hélène
H
Itzykson
Raphaël
R
Devergie
Agnès
A
Cumano
Ana
A
Gluckman
Eliane
E
Janin
Anne
A
Bandeira
Antonio
A
Socié
Gérard
G
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
D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2