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PMID: 16627754 Published · ppublish English Clinical Trial Journal Article Research Support, Non-U.S. Gov't

High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT.

Blood ·Vol. 108 ·No. 4 ·2006-08-15 ·Pages 1291-7

Rezvani K, Mielke S, Ahmadzadeh M, Kilical Y, Savani BN, Zeilah J, Keyvanfar K, Montero A, Hensel N, Kurlander R, Barrett AJ

Abstract

Regulatory T cells (T(reg)s) that constitutively express FOXP3 are instrumental to the maintenance of tolerance and may suppress graft-versus-host disease (GVHD) in humans. To determine whether regulatory T cells in allogeneic stem cell transplants (SCTs) ameliorate GVHD after transplantation, we quantitated the coexpression of FOXP3 on CD4(+) T cells in 32 donor SCTs infused into HLA-matched siblings and examined GVHD incidence in respective recipients. High CD4(+)FOXP3(+) T-cell count in the donor was associated with a reduced risk of GVHD. We monitored T(reg)s during immune reconstitution in 21 patients with leukemia undergoing a T-cell-depleted allogeneic SCT. Early after SCT, there was a significant expansion in the CD4(+)FOXP3(+) T-cell compartment. A low CD4(+)FOXP3(+) T-cell count early after SCT (day 30) was associated with an increased risk of GVHD, and the ratio of CD4(+)FOXP3(+) T cells to CD4(+)CD25(+)FOXP3(-) T cells was significantly reduced in patients with GVHD, suggesting diminished control of effector T cells. Our findings suggest that graft T(reg) content may predict for risk of GVHD after SCT. Determining the T(reg) levels in the donor and manipulating T(reg)s early after transplantation may provide a new approach to controlling GVHD.

MeSH Terms
Adolescent Adult CD4 Lymphocyte Count Female Forkhead Transcription Factors/immunology Graft vs Host Disease/blood,etiology,immunology,prevention & control Histocompatibility Testing Humans Leukemia/blood,complications,immunology,therapy Living Donors Male Risk Factors Stem Cell Transplantation T-Lymphocytes, Regulatory/immunology,transplantation Transplantation, Homologous
Chemicals
FOXP3 protein, human Forkhead Transcription Factors
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Rezvani Katayoun
Stem Cell Allogeneic Transplant Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1202, USA. [email protected]
Mielke Stephan
Ahmadzadeh Mojgan
Kilical Yasemin
Savani Bipin N
Zeilah Josette
Keyvanfar Keyvan
Montero Aldemar
Hensel Nancy
Kurlander Roger
Barrett A John
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2006-02-003996
Email
[email protected]
Published
2006-08-15
Epub
2006-00-20
Pages
1291-7
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1895877
Subset
IM
External Links
PubMed source DOI: 10.1182/blood-2006-02-003996 PMC Full Text View journal details
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