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Blood, 1 October 2004, Vol. 104, No. 7, pp. 2187-2193.
Prepublished online as a Blood First Edition Paper on June 1, 2004; DOI 10.1182/blood-2004-03-1040.


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TRANSPLANTATION

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

Yuji Miura, Christopher J. Thoburn, Emilie C. Bright, Michele L. Phelps, Tahiro Shin, Elizabeth C. Matsui, William H. Matsui, Sally Arai, Ephraim J. Fuchs, Georgia B. Vogelsang, Richard J. Jones, and Allan D. Hess

From the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; the Department of Pediatrics, Johns Hopkins University, Baltimore, MD; Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, Chicago, IL.

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)


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