Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD
Kathrin Rieger, Christoph Loddenkemper, Jochem Maul, Thomas Fietz, Daniel Wolff, Harald Terpe, Beate Steiner, Erika Berg, Stephan Miehlke, Martin Bornhäuser, Thomas Schneider, Martin Zeitz, Harald Stein, Eckhard Thiel, Rainer Duchmann, Lutz Uharek, Kathrin Rieger, Christoph Loddenkemper, Jochem Maul, Thomas Fietz, Daniel Wolff, Harald Terpe, Beate Steiner, Erika Berg, Stephan Miehlke, Martin Bornhäuser, Thomas Schneider, Martin Zeitz, Harald Stein, Eckhard Thiel, Rainer Duchmann, Lutz Uharek
Abstract
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.
Source: PubMed