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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1717-1723. Prepublished online as a Blood First Edition Paper on November 8, 2005; DOI 10.1182/blood-2005-06-2529.
TRANSPLANTATION Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHDFrom the Medical Clinic III, Hematology, Oncology, and Transfusion Medicine, the Consultation and Reference Center for Lymph Node Pathology and Hematopathology-Institute for Pathology, and Medical Clinic I, Gastroenterology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Berlin; the Division of Hematology and Oncology, and the Department of Pathology, University of Rostock, Rostock; and the Department of Gastroenterology and the Department of Hematology, University School of Medicine Dresden, Germany.
CD4+CD25+ regulatory T cells (Tregs) control immune responses to self- and foreign antigens and play a pivotal role in autoimmune diseases, infectious and noninfectious inflammation, and graft rejection. Since recent experimental studies have indicated that Tregs were able to ameliorate graft-versus-host disease (GvHD), we analyzed the number of infiltrating Tregs in the intestinal mucosa as one site of GvH reactivity using immunoenzymatic labeling to enumerate FOXP3+ T cells in 95 intestinal biopsies from 49 allografted patients in comparison with healthy controls and patients with infectious inflammation. While patients with cytomegalovirus (CMV)-colitis or diverticulitis showed a concomitant increase of CD8+ effectors and Tregs, acute and chronic GvHD were characterized by the complete lack of a counter-regulation indicated by a FOXP3+/CD8+ T-cell ratio identical to healthy controls. In contrast, specimens without histologic signs of GvHD demonstrated increased numbers of FOXP3+ per CD8+ T cells, indicating that the potential for Treg expansion is principally maintained in allografted patients. Our findings provide evidence that GvHD is associated with an insufficient up-regulation of Tregs in intestinal GvHD lesions. The determination of FOXP3+/CD8+ ratio can be a helpful tool to discriminate GvHD from infectious inflammation after allogeneic stem cell transplantation.
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