title: Functional regulatory T cells are collected in stem cell autografts by mobilization with high-dose cyclophosphamide and granulocyte colony-stimulating factor.
abstract: High-dose cyclophosphamide (Cy) and G-CSF are widely used to mobilize hemopoietic stem cells for treating patients with high-dose chemotherapy and autologous stem cell transplantation (ASCT). Because lymphocyte count in the graft collected after Cy-G-CSF treatment is an independent survival factor after ASCT for patients with multiple myeloma, our purpose was to study how Cy-G-CSF treatment affects the phenotype and function of T cells in patients with multiple myeloma. Cy induced a 3-fold decrease of T cell counts with a slow and partial T cell recovery of one-third at the time of hemopoietic stem cell collection. Cy-G-CSF treatment did not affect the relative ratios of central memory, effector memory, and late effector CD4+ or CD8+ T cells, but a decrease in the percentage of naive CD4+ cells was observed. The percentages of CD25+ cells increased 2- to 3-fold in CD4+ and CD8+ T cells, the former including both activated CD25low and CD25high cells. CD4+CD25high cells were regulatory T cells (Treg) that expressed high levels of FOXP3, CTLA-4, and GITR and displayed in vitro suppressive properties. The recovery of Treg absolute counts after Cy-G-CSF treatment was higher than the recovery of other lymphocyte subpopulations. In conclusion, Cy-G-CSF treatment induces a severe T cell count decrease without deleting Treg, which are potent inhibitors of antitumor response. The present data encourage novel therapeutic strategies to improve T cell recovery following ASCT while limiting Treg expansion.
authors.affiliation: Institute of Research in Biotherapy, Centre Hospitalier Universitaire (CHU) Montpellier, Montpellier, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Condomines
authors.forename: Philippe
authors.initials: P
authors.lastname: Quittet
authors.forename: Zhao-Yang
authors.initials: ZY
authors.lastname: Lu
authors.forename: Laure
authors.initials: L
authors.lastname: Nadal
authors.forename: Pascal
authors.initials: P
authors.lastname: Latry
authors.forename: Ernesto
authors.initials: E
authors.lastname: Lopez
authors.forename: Marion
authors.initials: M
authors.lastname: Baudard
authors.forename: Guilhem
authors.initials: G
authors.lastname: Requirand
authors.forename: Christophe
authors.initials: C
authors.lastname: Duperray
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Schved
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rossi
authors.forename: Karin
authors.initials: K
authors.lastname: Tarte
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007937:Leukapheresis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D033581:Stem Cell Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D014182:Transplantation, Autologous
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide