High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT.
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.
Rezvani
Katayoun
K
Stem Cell Allogeneic Transplant Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1202, USA. rezvanik@nhlbi.nih.gov
Mielke
Stephan
S
Ahmadzadeh
Mojgan
M
Kilical
Yasemin
Y
Savani
Bipin N
BN
Zeilah
Josette
J
Keyvanfar
Keyvan
K
Montero
Aldemar
A
Hensel
Nancy
N
Kurlander
Roger
R
Barrett
A John
AJ
D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006086:Graft vs Host Disease / Q000097:blood / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D006650:Histocompatibility Testing; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000628:therapy; D019520:Living Donors; D008297:Male; D012307:Risk Factors; D033581:Stem Cell Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D014184:Transplantation, Homologous
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors