title: Cyclosporine restores hematopoietic function by compensating for decreased Tregs in patients with pure red cell aplasia and acquired aplastic anemia.
abstract: Most patients with acquired pure red cell aplasia (PRCA) and some with acquired aplastic anemia (AA) respond well to cyclosporine (CsA), but thereafter often show CsA dependency. The mechanism underlying this dependency remains unknown. We established a reliable method for measuring the regulatory T cell (Treg) count using FoxP3 and Helios expression as markers and determined the balance between Tregs and other helper T cell subsets in 16 PRCA and 29 AA patients. The ratios of interferon-γ-producing CD4(+) (Th1) T cells to Tregs in untreated patients and CsA-dependent patients were significantly higher (PRCA 5.77 ± 1.47 and 7.38 ± 2.58; AA 6.18 ± 2.35 and 8.94 ± 4.06) than in healthy volunteers (HVs; 3.33 ± 0.90) due to the profound decrease in the percentage of Tregs. In contrast, the ratios were comparable to HVs in convalescent CsA-treated AA patients (4.74 ± 2.10) and AA patients in remission after the cessation of CsA treatment (4.24 ± 1.67). Low-dose CsA (100 ng/ml) inhibited the proliferation of conventional T cells (Tconv) to a similar degree to the inhibition by Tregs in a co-culture with a 1:1 Treg/Tconv ratio. The data suggest that CsA may reverse the hematopoietic suppression in PRCA and AA patients by compensating for the inadequate immune regulatory function that occurs due to a profound decrease in the Treg count.
authors.affiliation: Cellular Transplantation Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan.
authors.forename: An T T
authors.initials: AT
authors.lastname: Dao
authors.affiliation: Cellular Transplantation Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: Cellular Transplantation Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takamatsu
authors.affiliation: Department of Hematology, Ishikawa Prefectural Central Hospital, 2-1 Kuratsukihigashi, Kanazawa, Ishikawa, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Sugimori
authors.affiliation: Clinical Laboratory Science, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Katagiri
authors.affiliation: Cellular Transplantation Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Maruyama
authors.affiliation: Cellular Transplantation Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Zaimoku
authors.affiliation: Cellular Transplantation Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Maruyama
authors.affiliation: Cellular Transplantation Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan.
authors.forename: Trung Q
authors.initials: TQ
authors.lastname: Ly
authors.affiliation: Cellular Transplantation Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan.
authors.forename: Luis
authors.initials: L
authors.lastname: Espinoza
authors.affiliation: Cellular Transplantation Biology, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, 920-8641, Japan. snakao8205@staff.kanazawa-u.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D059425:Interferon-gamma Release Tests; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D012010:Red-Cell Aplasia, Pure / Q000188:drug therapy* / Q000276:immunology; D012074:Remission Induction; D012189:Retrospective Studies; D019966:Substance-Related Disorders / Q000209:etiology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D007166:Immunosuppressive Agents; D016572:Cyclosporine
keywords: Aplastic anemia; Cyclosporine A; Pure red cell aplasia; Regulatory T cells