title: Human regulatory T cells of G-CSF mobilized allogeneic stem cell donors qualify for clinical application.
abstract: Recent clinical studies demonstrate the high potency of regulatory T cells (Tregs) to control graft-versus-host disease in hematopoietic stem cell transplantation (SCT). However, the adoptive transfer of Tregs is limited by their low frequency in unstimulated donors and considerable concerns that G-CSF induced SC mobilization might have negative effects on the stability and function of Tregs. The isolation of Tregs from the G-CSF mobilized SC grafts would extend this novel strategy for tolerance induction to the unrelated setting and simplify global clinical application. We characterized CD4(+)CD25(high)CD127(-) Tregs from SC donors before and after G-CSF mobilization for their phenotype, function, and stability. After G-CSF application the Treg cell yield increased significantly. Donor Tregs retained their cytokine profile, phenotypic characteristics and in vitro expansion capacity after SC mobilization. Most importantly, in vivo G-CSF stimulated Tregs remained highly suppressive on the proliferation of effector T cells, also after in vitro expansion, and displayed a stable phenotype in epigenetic studies. The surface expression of CXCR3 is transiently reduced. However, donor-derived Tregs maintain their migratory properties after G-CSF stimulation. Therefore, the adoptive transfer of Tregs from G-CSF mobilized SC donors seems to be a feasible and safe strategy for clinical application in allogeneic SCT.
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: Lilia
authors.initials: L
authors.lastname: Goudeva
authors.forename: Philipp
authors.initials: P
authors.lastname: Ivanyi
authors.forename: Sven
authors.initials: S
authors.lastname: Olek
authors.forename: Christine S
authors.initials: CS
authors.lastname: Falk
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Anke
authors.initials: A
authors.lastname: Franzke
mesh_terms: D000328:Adult; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000187:drug effects*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014019:Tissue Donors; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D016179:Granulocyte Colony-Stimulating Factor