Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD.
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.
Rieger
Kathrin
K
Department of Hematology, Oncology and Transfusion Medicine, Charité-Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany. kathrin.rieger@charite.de
Loddenkemper
Christoph
C
Maul
Jochem
J
Fietz
Thomas
T
Wolff
Daniel
D
Terpe
Harald
H
Steiner
Beate
B
Berg
Erika
E
Miehlke
Stephan
S
Bornhäuser
Martin
M
Schneider
Thomas
T
Zeitz
Martin
M
Stein
Harald
H
Thiel
Eckhard
E
Duchmann
Rainer
R
Uharek
Lutz
L
D000208:Acute Disease; D015703:Antigens, CD / Q000032:analysis; D051927:CD24 Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D006801:Humans; D018928:Immunity, Mucosal; D007239:Infections / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000032:analysis; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology
D015703:Antigens, CD; D051927:CD24 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2