title: Stem cell source-dependent reconstitution of FOXP3+ T cells after pediatric SCT and the association with allo-reactive disease.
abstract: In adult patients, regulatory CD4+FOXP3+ T cells are suggested to have a role in the control of allo-reactive disease after hematopoietic SCT (HSCT). We compared CD4+FOXP3+ T-cell reconstitution after unrelated cord blood (UCB), matched unrelated donor (MUD) and matched sibling donor (MSD) HSCT in children, starting as early as 1 week after transplantation, and analyzed the association with allo-reactive disease. A total of 30 children were included who underwent a myeloablative-conditioning regimen followed by UCB (12/30), MUD (7/30) or MSD (11/30) HSCT. These three patient groups showed significant differences in FOXP3+ T-cell reconstitution pattern. Early after UCB and MSD, but not after MUD, HSCT a peak in FOXP3+ T cells was observed. There were significant differences in activation status and Ki67 expression of the FOXP3+ T cells after UCB and MSD, respectively. FOXP3+ T-cell proportions early after HSCT and in the graft were inversely correlated with allo-reactivity. This study indicates that FOXP3 reconstitution after HSCT is dependent on the type of graft used. Furthermore, in children evaluation of FOXP3+ T-cell numbers early after HSCT and in the graft may be used to judge the risk of developing allo-reactivity after HSCT.
authors.affiliation: Center for Molecular and Cellular Intervention (CMCI), University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: L L
authors.initials: LL
authors.lastname: Reubsaet
authors.forename: A P J
authors.initials: AP
authors.lastname: de Pagter
authors.forename: D
authors.initials: D
authors.lastname: van Baarle
authors.forename: L
authors.initials: L
authors.lastname: Keukens
authors.forename: N
authors.initials: N
authors.lastname: Nanlohy
authors.forename: E A M
authors.initials: EA
authors.lastname: Sanders
authors.forename: B J
authors.initials: BJ
authors.lastname: Prakken
authors.forename: J J
authors.initials: JJ
authors.lastname: Boelens
authors.forename: I M
authors.initials: IM
authors.lastname: de Kleer
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007223:Infant; D019394:Ki-67 Antigen / Q000276:immunology; D008297:Male; D035781:Siblings; D014184:Transplantation, Homologous; D061349:Unrelated Donors
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen