title: Acute but not chronic graft-versus-host disease is associated with a reduction of circulating CD4(+)CD25 (high)CD127 (low/-) regulatory T cells.
abstract: Defects in central and peripheral tolerance are thought to contribute to life-threatening graft-versus-host disease (GvHD), a severe complication following allogeneic stem cell transplantation (SCT). Recent investigations have demonstrated regulatory T cells (Tregs) to suppress allogeneic immune reactions. Therefore, SCT patients with no or critically low numbers of Tregs may have an increased risk of GvHD. To address this hypothesis, we analyzed the recovery of CD4(+)CD25(high)CD127(low/-) Tregs in the peripheral blood of patients who have never developed GvHD (n = 6), patients who developed acute/chronic GvHD (n = 18), and patients who developed chronic GvHD without an earlier acute manifestation (n = 5) every 30 days for the first 6 months after peripheral blood SCT (PBSCT). The number of Tregs continuously improved in acute/chronic GvHD patients, but always remained lower than Tregs quantified in patients who never developed a GvHD. In contrast, chronic GvHD patients who did not develop acute GvHD earlier displayed significantly increased Treg cell numbers at the timepoint of chronic inflammation. These results indicate that numerically deficient Tregs following PBSCT are associated with the development of acute but not chronic GvHD.
authors.affiliation: Department of Haematology, Haemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
authors.forename: Sya N
authors.initials: SN
authors.lastname: Ukena
authors.forename: Jens
authors.initials: J
authors.lastname: Grosse
authors.forename: Eva
authors.initials: E
authors.lastname: Mischak-Weissinger
authors.forename: Stefanie
authors.initials: S
authors.lastname: Buchholz
authors.forename: Michael
authors.initials: M
authors.lastname: Stadler
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Anke
authors.initials: A
authors.lastname: Franzke
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use; D033581:Stem Cell Transplantation / Q000009:adverse effects; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D011239:Prednisolone