title: Advanced flowcytometric analysis of regulatory T cells: CD127 downregulation early post stem cell transplantation and altered Treg/CD3(+)CD4(+)-ratio in severe GvHD or relapse.
abstract: Regulatory T cells (Tregs) are of crucial importance to suppress graft versus host disease (GvHD) post allogeneic stem cell transplantation (SCT), but are also known to impair antitumor immunity. However, Treg longitudinal studies are rare and in this respect advanced flowcytometric approaches for Treg characterization are necessary. To investigate the relation of both the percentage and the absolute numbers of Tregs on GvHD or relapse we measured CD4(+)CD25(+/hi)CD127(lo/-) Tregs in 239 peripheral blood (PB) samples of 16 patients during the first two years post-SCT. A 10-color flowcytometric panel was established to evaluate Treg subpopulations and has been tested in ten healthy individuals. In patients we demonstrated a decrease in CD127 expression on T cells early post-SCT which increases during the first year. Moreover, Tregs reached higher absolute numbers in patients with GvHD≤grade I compared to those with GvHD grades II-IV. In contrast, the percentage of Tregs was significantly higher in patients with GvHD grades II-IV or disease relapse compared to those without GvHD. These patients fit into the range of healthy individuals where a median value of 7.5% and 6.4% of T helper cells were characterized as CD4(+)CD25(+/hi)CD127(lo/-) and CD4(+)CD25(+/hi) Tregs, respectively. Furthermore, Tregs could be further subdivided into 40% naïve, 51% central memory and 9% effector memory Tregs. Our results showed for the first time a downregulation of CD127 expression on T cells including Tregs in patients early post-SCT. Additionally, new insights into the recovery of Tregs regarding GvHD and relapse were provided.
authors.affiliation: Pediatric Hematology and Oncology, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, Frankfurt, Germany. melanie.bremm@kgu.de
authors.forename: Melanie
authors.initials: M
authors.lastname: Bremm
authors.forename: Sabine
authors.initials: S
authors.lastname: Huenecke
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
authors.forename: Eva
authors.initials: E
authors.lastname: Ponstingl
authors.forename: Regine
authors.initials: R
authors.lastname: Mueller
authors.forename: Annekathrin
authors.initials: A
authors.lastname: Heinze
authors.forename: Gesine
authors.initials: G
authors.lastname: Bug
authors.forename: Andrea
authors.initials: A
authors.lastname: Quaiser
authors.forename: Michael
authors.initials: M
authors.lastname: Kapinsky
authors.forename: Claudia
authors.initials: C
authors.lastname: Brehm
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koehl
mesh_terms: D000293:Adolescent; D000328:Adult; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006086:Graft vs Host Disease / Q000097:blood / Q000209:etiology / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D017252:CD3 Complex; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit