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01-04-2016 | Original Article

Cyclosporine restores hematopoietic function by compensating for decreased Tregs in patients with pure red cell aplasia and acquired aplastic anemia

Authors: An T. T. Dao, Hirohito Yamazaki, Hiroyuki Takamatsu, Chiharu Sugimori, Takamasa Katagiri, Hiroyuki Maruyama, Yoshitaka Zaimoku, Kana Maruyama, Trung Q. Ly, Luis Espinoza, Shinji Nakao

Published in: Annals of Hematology | Issue 5/2016

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.

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Title: Cyclosporine restores hematopoietic function by compensating for decreased Tregs in patients with pure red cell aplasia and acquired aplastic anemia
Authors: An T. T. Dao
Hirohito Yamazaki
Hiroyuki Takamatsu
Chiharu Sugimori
Takamasa Katagiri
Hiroyuki Maruyama
Yoshitaka Zaimoku
Kana Maruyama
Trung Q. Ly
Luis Espinoza
Shinji Nakao
Publication date: 01-04-2016
Publisher: Springer Berlin Heidelberg
Published in: Annals of Hematology / Issue 5/2016
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-016-2629-7

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