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

Annals of Hematology

Volumn 95, Issue 5, 2016, Pages 771-781

  Dao, An T T ^a   Yamazaki, Hirohito ^a   Takamatsu, Hiroyuki ^a   Sugimori, Chiharu ^b   Katagiri, Takamasa ^a   Maruyama, Hiroyuki ^a   Zaimoku, Yoshitaka ^a   Maruyama, Kana ^a   Ly, Trung Q ^a   Espinoza, Luis ^a   Nakao, Shinji ^a  

^a KANAZAWA UNIVERSITY   (Japan)

^b ISHIKAWA PREFECTURAL CENTRAL HOSPITAL   (Japan)

Author keywords

Aplastic anemia; Cyclosporine A; Pure red cell aplasia; Regulatory T cells

Indexed keywords

CHEMOKINE RECEPTOR CCR4; CYCLOSPORIN A; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GAMMA INTERFERON; INTERLEUKIN 17; INTERLEUKIN 2; PROTEIN; PROTEIN HELIOS; TRANSCRIPTION FACTOR FOXP3; UNCLASSIFIED DRUG; CYCLOSPORIN; IMMUNOSUPPRESSIVE AGENT; T LYMPHOCYTE ANTIGEN;

ADULT; AGED; ANTIPROLIFERATIVE ACTIVITY; APLASTIC ANEMIA; ARTICLE; CD3+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CLINICAL ARTICLE; COCULTURE; CONTROLLED STUDY; CONVALESCENCE; CYTOKINE RELEASE; FEMALE; FLOW CYTOMETRY; HEMATOPOIESIS; HUMAN; HUMAN CELL; LYMPHOCYTE COUNT; MALE; MIDDLE AGED; PRIORITY JOURNAL; PURE RED CELL ANEMIA; REGULATORY T LYMPHOCYTE; REMISSION; T LYMPHOCYTE SUBPOPULATION; TH1 CELL; TH17 CELL; TH2 CELL; VERY ELDERLY; ANEMIA, APLASTIC; COMPARATIVE STUDY; DRUG EFFECTS; HELPER CELL; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; IMMUNOPHENOTYPING; INTERFERON GAMMA RELEASE ASSAY; PATHOLOGY; RED-CELL APLASIA, PURE; RETROSPECTIVE STUDY; SUBSTANCE-RELATED DISORDERS;

ADULT; AGED; AGED, 80 AND OVER; ANEMIA, APLASTIC; ANTIGENS, DIFFERENTIATION, T-LYMPHOCYTE; CYCLOSPORINE; FEMALE; FLOW CYTOMETRY; HEMATOPOIESIS; HUMANS; IMMUNE TOLERANCE; IMMUNOPHENOTYPING; IMMUNOSUPPRESSIVE AGENTS; INTERFERON-GAMMA RELEASE TESTS; LYMPHOCYTE COUNT; MALE; MIDDLE AGED; RED-CELL APLASIA, PURE; REMISSION INDUCTION; RETROSPECTIVE STUDIES; SUBSTANCE-RELATED DISORDERS; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, HELPER-INDUCER; T-LYMPHOCYTES, REGULATORY;

EID: 84960336347     PISSN: 09395555     EISSN: 14320584     Source Type: Journal    
DOI: 10.1007/s00277-016-2629-7     Document Type: Article

References (43)

1. Nitta H, Mihara K, Sakai A, Kimura A (2010) Expansion of CD8+ /perforin+ effector memory T cells in the bone marrow of patients with thymoma-associated pure red cell aplasia. Br J Haematol 150(6):712–715. doi:10.1111/j.1365-2141.2010.08273.x
2. Nitta H, Harada Y, Hyodo H, Kimura A, Harada H (2012) Expansion of CD8+/perforin+ T-cells predicts response to ciclosporin A therapy in patients with erythroid hypoplasia/aplasia. Br J Haematol 157(5):641–645. doi:10.1111/j.1365-2141.2012.09057.x
3. Michishita Y, Hirokawa M, Fujishima N, Abe Y, Fujishima M, Guo YM, Ubukawa K, Liu J, Yoshioka T, Kameoka Y, Saitoh H, Tagawa H, Takahashi N, Sawada K (2013) CDR3-independent expansion of Vdelta1 T lymphocytes in acquired chronic pure red cell aplasia. Immunol Lett 150(1–2):23–29. doi:10.1016/j.imlet.2012.12.006
4. Fujishima N, Hirokawa M, Fujishima M, Wada C, Toyoshima I, Watanabe S, Sawada K (2006) Oligoclonal T cell expansion in blood but not in the thymus from a patient with thymoma-associated pure red cell aplasia. Haematologica 91(12 Suppl):ECR47
5. Shinohara K, Mitani N, Miyazaki M, Sakuragi S, Matsuda K, Ogawara S, Saito T, Kaneoka H, Ooji T (2005) Pure red-cell aplasia caused by the antibody to recombinant erythropoietin, epoetin-beta, in a Japanese patient with chronic renal failure. Am J Hematol 78(1):15–20. doi:10.1002/ajh.20245
6. Aljama P, Carracedo J, Madueno JA, Ramirez R, Martin-Malo A, de Francisco AL M (2005) Antibody-mediated pure red cell aplasia (PRCA): ensuring future progress by collecting data from a registry. Nephrol Dial Transplant: Off Publ Eur Dial Transplant Assoc Eur Ren Assoc 20(Suppl 4):iv27-30. doi:10.1093/ndt/gfh1089
7. Sawada K, Hirokawa M, Fujishima N, Teramura M, Bessho M, Dan K, Tsurumi H, Nakao S, Urabe A, Omine M, Ozawa K, Group PCS (2007) Long-term outcome of patients with acquired primary idiopathic pure red cell aplasia receiving cyclosporine A. A nationwide cohort study in Japan for the PRCA Collaborative Study Group. Haematologica 92(8):1021–1028
8. Saracco P, Quarello P, Iori AP, Zecca M, Longoni D, Svahn J, Varotto S, Del Vecchio GC, Dufour C, Ramenghi U, Bacigalupo A, Locasciulli A, Bone Marrow Failure Study Group of the A (2008) Cyclosporin A response and dependence in children with acquired aplastic anaemia: a multicentre retrospective study with long-term observation follow-up. Br J Haematol 140(2):197–205. doi:10.1111/j.1365-2141.2007.06903.x
9. Nakao S, Takamatsu H, Chuhjo T, Ueda M, Shiobara S, Matsuda T, Kaneshige T, Mizoguchi H (1994) Identification of a specific HLA class II haplotype strongly associated with susceptibility to cyclosporine-dependent aplastic anemia. Blood 84(12):4257–4261
10. Buckner JH (2010) Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol 10(12):849–859. doi:10.1038/nri2889
11. Sakaguchi S, Ono M, Setoguchi R, Yagi H, Hori S, Fehervari Z, Shimizu J, Takahashi T, Nomura T (2006) Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev 212:8–27. doi:10.1111/j.0105-2896.2006.00427.x
12. Kordasti S, Marsh J, Al-Khan S, Jiang J, Smith A, Mohamedali A, Abellan PP, Veen C, Costantini B, Kulasekararaj AG, Benson-Quarm N, Seidl T, Mian SA, Farzaneh F, Mufti GJ (2012) Functional characterization of CD4+ T cells in aplastic anemia. Blood 119(9):2033–2043. doi:10.1182/blood-2011-08-368308
13. Shi J, Ge M, Lu S, Li X, Shao Y, Huang J, Huang Z, Zhang J, Nie N, Zheng Y (2012) Intrinsic impairment of CD4(+)CD25(+) regulatory T cells in acquired aplastic anemia. Blood 120(8):1624–1632. doi:10.1182/blood-2011-11-390708
14. Kim YC, Bhairavabhotla R, Yoon J, Golding A, Thornton AM, Tran DQ, Shevach EM (2012) Oligodeoxynucleotides stabilize Helios-expressing Foxp3+ human T regulatory cells during in vitro expansion. Blood 119(12):2810–2818. doi:10.1182/blood-2011-09-377895
15. Raffin C, Pignon P, Celse C, Debien E, Valmori D, Ayyoub M (2013) Human memory Helios− FOXP3+ regulatory T cells (Tregs) encompass induced Tregs that express Aiolos and respond to IL-1beta by downregulating their suppressor functions. J Immunol 191(9):4619–4627. doi:10.4049/jimmunol.1301378
16. Golding A, Hasni S, Illei G, Shevach EM (2013) The percentage of FoxP3+Helios+ Treg cells correlates positively with disease activity in systemic lupus erythematosus. Arthritis Rheum 65(11):2898–2906. doi:10.1002/art.38119
17. Bin Dhuban K, d’Hennezel E, Nashi E, Bar-Or A, Rieder S, Shevach EM, Nagata S, Piccirillo CA (2015) Coexpression of TIGIT and FCRL3 identifies Helios+ human memory regulatory T cells. J Immunol 194(8):3687–3696. doi:10.4049/jimmunol.1401803
18. Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A, Parizot C, Taflin C, Heike T, Valeyre D, Mathian A, Nakahata T, Yamaguchi T, Nomura T, Ono M, Amoura Z, Gorochov G, Sakaguchi S (2009) Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30(6):899–911. doi:10.1016/j.immuni.2009.03.019
19. Solomou EE, Rezvani K, Mielke S, Malide D, Keyvanfar K, Visconte V, Kajigaya S, Barrett AJ, Young NS (2007) Deficient CD4+ CD25+ FOXP3+ T regulatory cells in acquired aplastic anemia. Blood 110(5):1603–1606. doi:10.1182/blood-2007-01-066258
20. de Latour RP, Visconte V, Takaku T, Wu C, Erie AJ, Sarcon AK, Desierto MJ, Scheinberg P, Keyvanfar K, Nunez O, Chen J, Young NS (2010) Th17 immune responses contribute to the pathophysiology of aplastic anemia. Blood 116(20):4175–4184. doi:10.1182/blood-2010-01-266098
21. Ryba-Stanislawowska M, Rybarczyk-Kapturska K, Mysliwiec M, Mysliwska J (2014) Elevated levels of serum IL-12 and IL-18 are associated with lower frequencies of CD4(+)CD25 (high)FOXP3 (+) regulatory T cells in young patients with type 1 diabetes. Inflammation 37(5):1513–1520. doi:10.1007/s10753-014-9878-1
22. Bovenschen HJ, van de Kerkhof PC, van Erp PE, Woestenenk R, Joosten I, Koenen HJ (2011) Foxp3+ regulatory T cells of psoriasis patients easily differentiate into IL-17A-producing cells and are found in lesional skin. J Invest Dermatol 131(9):1853–1860. doi:10.1038/jid.2011.139
23. Bovenschen HJ, van Vlijmen-Willems IM, van de Kerkhof PC, van Erp PE (2006) Identification of lesional CD4+ CD25+ Foxp3+ regulatory T cells in psoriasis. Dermatology 213(2):111–117. doi:10.1159/000093849
24. Thornton AM, Korty PE, Tran DQ, Wohlfert EA, Murray PE, Belkaid Y, Shevach EM (2010) Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J Immunol 184(7):3433–3441. doi:10.4049/jimmunol.0904028
25. Himmel ME, MacDonald KG, Garcia RV, Steiner TS, Levings MK (2013) Helios+ and Helios− cells coexist within the natural FOXP3+ T regulatory cell subset in humans. J Immunol 190(5):2001–2008. doi:10.4049/jimmunol.1201379
26. Coenen JJ, Koenen HJ, van Rijssen E, Hilbrands LB, Joosten I (2006) Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells. Blood 107(3):1018–1023. doi:10.1182/blood-2005-07-3032
27. Zeiser R, Nguyen VH, Beilhack A, Buess M, Schulz S, Baker J, Contag CH, Negrin RS (2006) Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood 108(1):390–399. doi:10.1182/blood-2006-01-0329
28. Baumgrass R, Brandt C, Wegner F, Abdollahnia M, Worm M (2010) Low-dose, but not high-dose, cyclosporin A promotes regulatory T-cell induction, expansion, or both. J Allergy Clin Immunol 126(1):183–184. doi:10.1016/j.jaci.2010.04.032, author reply 184
29. Brandt C, Pavlovic V, Radbruch A, Worm M, Baumgrass R (2009) Low-dose cyclosporine A therapy increases the regulatory T cell population in patients with atopic dermatitis. Allergy 64(11):1588–1596. doi:10.1111/j.1398-9995.2009.02054.x
30. Kawai M, Kitade H, Mathieu C, Waer M, Pirenne J (2005) Inhibitory and stimulatory effects of cyclosporine A on the development of regulatory T cells in vivo. Transplantation 79(9):1073–1077
31. Fanigliulo D, Lazzerini PE, Capecchi PL, Ulivieri C, Baldari CT, Laghi-Pasini F (2015) Clinically-relevant cyclosporin and rapamycin concentrations enhance regulatory T cell function to a similar extent but with different mechanisms: an in-vitro study in healthy humans. Int Immunopharmacol 24(2):276–284. doi:10.1016/j.intimp.2014.12.021
32. Fujisao S, Tsuda H (1998) Th1/Th2 balance alteration in the clinical course of a patient with pure red cell aplasia and thymoma. Br J Haematol 103(2):308–310
33. Alunno A, Manetti M, Caterbi S, Ibba-Manneschi L, Bistoni O, Bartoloni E, Valentini V, Terenzi R, Gerli R (2015) Altered immunoregulation in rheumatoid arthritis: the role of regulatory T cells and proinflammatory th17 cells and therapeutic implications. Mediat Inflamm 2015:751793. doi:10.1155/2015/751793
34. Noack M, Miossec P (2014) Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev 13(6):668–677. doi:10.1016/j.autrev.2013.12.004
35. Dolff S, Bijl M, Huitema MG, Limburg PC, Kallenberg CG, Abdulahad WH (2011) Disturbed Th1, Th2, Th17 and T(reg) balance in patients with systemic lupus erythematosus. Clin Immunol 141(2):197–204. doi:10.1016/j.clim.2011.08.005
36. Buc M (2013) Role of regulatory T cells in pathogenesis and biological therapy of multiple sclerosis. Mediat Inflamm 2013:963748. doi:10.1155/2013/963748
37. Sawada K, Fujishima N, Hirokawa M (2008) Acquired pure red cell aplasia: updated review of treatment. Br J Haematol 142(4):505–514. doi:10.1111/j.1365-2141.2008.07216.x
38. Hirokawa M, Sawada K, Fujishima N, Nakao S, Urabe A, Dan K, Fujisawa S, Yonemura Y, Kawano F, Omine M, Ozawa K, Group PCS (2008) Long-term response and outcome following immunosuppressive therapy in thymoma-associated pure red cell aplasia: a nationwide cohort study in Japan by the PRCA collaborative study group. Haematologica 93(1):27–33. doi:10.3324/haematol.11655
39. Philippe M, Henin E, Bertrand Y, Plantaz D, Goutelle S, Bleyzac N (2015) Model-based determination of effective blood concentrations of cyclosporine for neutrophil response in the treatment of severe aplastic anemia in children. AAPS J 17(5):1157–1167. doi:10.1208/s12248-015-9779-8
40. Samson M, Audia S, Janikashvili N, Ciudad M, Trad M, Fraszczak J, Ornetti P, Maillefert JF, Miossec P, Bonnotte B (2012) Brief report: inhibition of interleukin-6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis. Arthritis Rheum 64(8):2499–2503. doi:10.1002/art.34477
41. Bell CJ, Sun Y, Nowak UM, Clark J, Howlett S, Pekalski ML, Yang X, Ast O, Waldhauer I, Freimoser-Grundschober A, Moessner E, Umana P, Klein C, Hosse RJ, Wicker LS, Peterson LB (2015) Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells. J Autoimmun 56:66–80. doi:10.1016/j.jaut.2014.10.002
42. Zorn E, Nelson EA, Mohseni M, Porcheray F, Kim H, Litsa D, Bellucci R, Raderschall E, Canning C, Soiffer RJ, Frank DA, Ritz J (2006) IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo. Blood 108(5):1571–1579. doi:10.1182/blood-2006-02-004747
43. Xia J, Liu W, Hu B, Tian Z, Yang Y (2010) IL-15 promotes regulatory T cell function and protects against diabetes development in NK-depleted NOD mice. Clin Immunol 134(2):130–139. doi:10.1016/j.clim.2009.09.011