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

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...

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Bibliographic Details
Published in:	Annals of hematology 2016-04, Vol.95 (5), p.771-781
Main Authors:	Dao, An T. T., Yamazaki, Hirohito, Takamatsu, Hiroyuki, Sugimori, Chiharu, Katagiri, Takamasa, Maruyama, Hiroyuki, Zaimoku, Yoshitaka, Maruyama, Kana, Ly, Trung Q., Espinoza, Luis, Nakao, Shinji
Format:	Article
Language:	eng
Subjects:	Adult Aged Aged, 80 and over Anemia, Aplastic - drug therapy Anemia, Aplastic - immunology Antigens, Differentiation, T-Lymphocyte - analysis Cyclosporine - pharmacology Cyclosporine - therapeutic use Female Flow Cytometry Hematology Hematopoiesis - drug effects Hematopoiesis - immunology Humans Immune Tolerance Immunophenotyping Immunosuppressive Agents - pharmacology Immunosuppressive Agents - therapeutic use Interferon-gamma Release Tests Lymphocyte Count Male Medicine Medicine & Public Health Middle Aged Oncology Original Article Red-Cell Aplasia, Pure - drug therapy Red-Cell Aplasia, Pure - immunology Remission Induction Retrospective Studies Substance-Related Disorders - etiology Substance-Related Disorders - immunology T-Lymphocyte Subsets - immunology T-Lymphocytes, Helper-Inducer - immunology T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - pathology
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Summary:	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.
ISSN:	0939-5555 1432-0584