Association of Foxp3 regulatory gene expression with graft-versus-host disease

• Published in: Blood 2004-10, Vol.104 (7), p.2187-2193
• Main Authors: Miura, Yuji, Thoburn, Christopher J., Bright, Emilie C., Phelps, Michele L., Shin, Tahiro, Matsui, Elizabeth C., Matsui, William H., Arai, Sally, Fuchs, Ephraim J., Vogelsang, Georgia B., Jones, Richard J., Hess, Allan D.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone Marrow Cells - metabolism; Bone Marrow Transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - metabolism; Cell Membrane - metabolism; DNA-Binding Proteins - genetics; Female; Forkhead Transcription Factors; Gene Expression Regulation; Graft vs Host Disease - genetics; Humans; Leukocytes, Mononuclear - metabolism; Male; Medical sciences; Middle Aged; Receptors, Interleukin-2 - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Stem Cell Transplantation; T-Lymphocytes - metabolism; Thymidine - chemistry; Thymus Gland - metabolism; Time Factors; Transcription, Genetic; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-03-1040

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. (Blood. 2004;104:2187-2193)