Association of Foxp3 regulatory gene expression with graft-versus-host disease.
Graft-versus-host disease (GVHD) is characterized by an impairment of mechanisms that underlie the development of immunologic tolerance. Although the cytokine storm associated with GVHD leads to expression of cell surface markers on both effector and regulatory T cells, regulatory CD4+ T cells that play an instrumental role in the maintenance of tolerance appear to uniquely express the Foxp3 transcriptional repressor. Foxp3 mRNA expression was significantly decreased in peripheral blood mononuclear cells from patients with either allogeneic GVHD or autologous GVHD compared with patients without GVHD. Expression of Foxp3 negatively correlated with the severity of GVHD but positively correlated with recent thymic emigrants. The results suggest that defective thymic function contributes to the impaired reconstitution of immune regulatory mechanisms following transplantation. The decrease in regulatory mechanisms after transplantation appears to provide an environment permissive to the development of GVHD.
Miura
Yuji
Y
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
Thoburn
Christopher J
CJ
Bright
Emilie C
EC
Phelps
Michele L
ML
Shin
Tahiro
T
Matsui
Elizabeth C
EC
Matsui
William H
WH
Arai
Sally
S
Fuchs
Ephraim J
EJ
Vogelsang
Georgia B
GB
Jones
Richard J
RJ
Hess
Allan D
AD
D000293:Adolescent; D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000378:metabolism; D013936:Thymidine / Q000737:chemistry; D013950:Thymus Gland / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D013936:Thymidine