title: Human regulatory T cells in allogeneic stem cell transplantation.
abstract: GVHD is still one of the major complications after allogeneic stem cell transplantation. Whereas murine data have clearly shown the beneficial effects of regulatory T cells (Tregs) on the prevention of GVHD, data from the human system are rare. Here, we present a comparative dynamic analysis of CD4(+)CD25(hi)CD127(lo/-) Tregs from patients with and without GVHD analyzing the whole genome profile over the first 6 months after stem cell transplantation, representing the most sensitive time window for tolerance induction. The Treg transcriptome showed a high stability. However, the comparison of Treg transcriptomes from patients with and without GVHD uncovered regulated gene transcripts highly relevant for Treg cell function. The confirmative protein analyses demonstrated a significantly higher expression of granzyme A, CXCR3, and CCR5 in Tregs of immune tolerant patients. These results point to a reduced suppressive function of Tregs from GVHD patients with diminished migration capacity to the target organs.
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Sya N
authors.initials: SN
authors.lastname: Ukena
authors.forename: Sarvari
authors.initials: S
authors.lastname: Velaga
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.forename: Jens
authors.initials: J
authors.lastname: Grosse
authors.forename: Udo
authors.initials: U
authors.lastname: Baron
authors.forename: Stefanie
authors.initials: S
authors.lastname: Buchholz
authors.forename: Michael
authors.initials: M
authors.lastname: Stadler
authors.forename: Dunja
authors.initials: D
authors.lastname: Bruder
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Anke
authors.initials: A
authors.lastname: Franzke
mesh_terms: D006086:Graft vs Host Disease / Q000276:immunology; D006801:Humans; D033581:Stem Cell Transplantation / Q000379:methods; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*; D014181:Transplantation Immunology / Q000502:physiology*; D014184:Transplantation, Homologous