The effects of leflunomide on CD4 +CD25 +Foxp3 + T regulatory cells in mice receiving allogeneic bone marrow transplantation

Inflammation Research

Volumn 61, Issue 1, 2012, Pages 53-60

  Jin, Di ^a,b   Duan, Kaizhong ^a   Zhang, Lianjun ^a   Peng, Jianxia ^a   Zhao, Yong ^a,b  

^a INSTITUTE OF ZOOLOGY   (China)

^b UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

Author keywords

Autoimmune diseases; Bone marrow transplantation; CD4 +CD25 +Foxp3 + Treg cells; Foxp3; Leflunomide

Indexed keywords

CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GLUCOCORTICOID INDUCED TUMOR NECROSIS FACTOR RECEPTOR; LEFLUNOMIDE; TRANSCRIPTION FACTOR FOXP3;

ALLOGENIC BONE MARROW TRANSPLANTATION; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; AUTOIMMUNE DISEASE; BAGG ALBINO MOUSE; BLOOD DONOR; BONE MARROW CELL; C57BL 6 MOUSE; CD4+ CD25+ FOXP3+ REGULATORY T LYMPHOCYTE; CD4+ CD25+ REGULATORY T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; FEMALE; GRAFT RECIPIENT; GRAFT REJECTION; IMMUNOLOGICAL TOLERANCE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; SPLEEN; THYMOCYTE; TREATMENT DURATION; WHOLE BODY RADIATION;

ANIMALS; ANTIBODIES, MONOCLONAL; AUTOIMMUNE DISEASES; BONE MARROW TRANSPLANTATION; CD4-POSITIVE T-LYMPHOCYTES; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; ISOXAZOLES; LEUKOCYTES, MONONUCLEAR; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; T-LYMPHOCYTES, REGULATORY;

EID: 84857626144     PISSN: 10233830     EISSN: 1420908X     Source Type: Journal    
DOI: 10.1007/s00011-011-0388-4     Document Type: Article

References (48)

1. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and nonself. Nat Immunol. 2005;6:345-52. (Pubitemid 41716771)
2. Billiard F, Litvinova E, Saadoun D, Djelti F, Klatzmann D, Cohen JL, Marodon G, Salomon BL. Regulatory and effector T cell activation levels are prime determinants of in vivo immune regulation. J Immunol. 2006;177:2167-74. (Pubitemid 44200975)
3. Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S, Nochy D, Debre P, Piette JC, Gorochov G. Global natural regulatory T cell depletion in active systemic lupus erythematosus. J Immunol. 2005;175:8392-400. (Pubitemid 41798406)
4. Paust S, Cantor H. Regulatory T cells and autoimmune disease. Immunol Rev. 2005;204:195-207. (Pubitemid 40460503)
5. Lindley S, Dayan CM, Bishop A, Roep BO, Peakman M, Tree TI. Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes. 2005;54:92-9. (Pubitemid 40105099)
6. Gartner D, Hoff H, Gimsa U, Burmester GR, Brunner-Weinzierl MC. CD25 regulatory T cells determine secondary but not primary remission in EAE: impact on long-term disease progression. J Neuroimmunol. 2006;172:73-84. (Pubitemid 43277492)
7. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4:330-6. (Pubitemid 36432314)
8. Sakaguchi S. The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery. J Clin Invest. 2003;112:1310-2. (Pubitemid 38057683)
9. Zhang L, Yi H, Xia XP, Zhao Y. Transforming growth factorbeta: an important role in CD4?CD25? regulatory T cells and immune tolerance. Autoimmunity. 2006;39:269-76. (Pubitemid 44203503)
10. Campbell DJ, Ziegler SF. FOXP3 modifies the phenotypic and functional properties of regulatory T cells. Nat Rev Immunol. 2007;7:305-10. (Pubitemid 46480960)
11. Ikehara S. Bone marrow transplantation: a new strategy for intractable diseases. Drugs Today (Barc). 2002;38:103-11. (Pubitemid 34269361)
12. Nakagawa T, Nagata N, Hosaka N, Ogawa R, Nakamura K, Ikehara S. Prevention of autoimmune inflammatory polyarthritis in male New Zealand black/KN mice by transplantation of bone marrow cells plus bone (stromal cells). Arthritis Rheum. 1993;36:263-8. (Pubitemid 23059341)
13. Rezvani K, Mielke S, Ahmadzadeh M, Kilical Y, Savani BN, Zeilah J, Keyvanfar K, Montero A, Hensel N, Kurlander R, Barrett AJ. High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLAmatched allogeneic SCT. Blood. 2006;108:1291-7. (Pubitemid 44232027)
14. Strauss L, Czystowska M, Szajnik M, Mandapathil M, Whiteside TL. Differential responses of human regulatory T cells (Treg) and effector T cells to rapamycin. PLoS One. 2009;4:e5994.
15. Schattenkirchner M. The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review. Immunopharmacology. 2000;47:291-8. (Pubitemid 30394544)
16. Johansen A, Jensen JE, Horn HC, Nielsen B, Kemp E. Effect of leflunomide and cyclosporine on graft survival and changes in lymphocyte phenotypes in a rat heart allotransplantation model. Transpl Immunol. 1998;6:48-52. (Pubitemid 28288596)
17. He C, Lu X, Yan Z, Wu M, Liu S, Yu Y, Luo P (2010) Therapeutic effect of leflunomide on the development of experimental lupus nephritis in mice. Rheumatol Int [Epub ahead of print] doi: 10.1007/s00296-010-1630-z
18. Snydman DR. Leflunomide: a small step forward in meeting the urgent need for treatment of drug-resistant cytomegalovirus infection. Transplantation. 2010;90:362-3.
19. Orden AO, Chuluyan JC, Colombini AC, Barbera RF (2011) Leflunomide use in a cytomegalovirus infection of a patient with dermatomyositis. Rheumatol Int [Epub ahead of print] doi: 10.1007/s00296-010-1786-6
20. Avery RK, Mossad SB, Poggio E, Lard M, Budev M, Bolwell B, Waldman WJ, Braun W, Mawhorter SD, Fatica R, Krishnamurthi V, Young JB, Shrestha R, Stephany B, Lurain N, Yen-Lieberman B. Utility of leflunomide in the treatment of complex cytomegalovirus syndromes. Transplantation. 2010;90:419-26.
21. Liacini A, Seamone ME, Muruve DA, Tibbles LA. Anti-BK virus mechanisms of sirolimus and leflunomide alone and in combination: toward a new therapy for BK virus infection. Transplantation. 2010;90:1450-7.
22. Hail N Jr, Chen P, Bushman LR. Teriflunomide (leflunomide) promotes cytostatic, antioxidant, and apoptotic effects in transformed prostate epithelial cells: evidence supporting a role for teriflunomide in prostate cancer chemoprevention. Neoplasia. 2010;12:464-75.
23. Xu X, Williams JW, Bremer EG, Finnegan A, Chong AS. Inhibition of protein tyrosine phosphorylation in T cells by a novel immunosuppressive agent, leflunomide. J Biol Chem. 1995;270: 12398-403.
24. Williamson RA, Yea CM, Robson PA, Curnock AP, Gadher S, Hambleton AB, Woodward K, Bruneau JM, Hambleton P, Moss D, Thomson TA, Spinella-Jaegle S, Morand P, Courtin O, Sautes C, Westwood R, Hercend T, Kuo EA, Ruuth E. Dihydroorotate dehydrogenase is a high affinity binding protein for A77 1726 and mediator of a range of biological effects of the immunomodulatory compound. J Biol Chem. 1995;270:22467-72.
25. Kutluana U, Oruc N, Nart D, Kaptanoglu B, Yonetci N, Ozutemiz O. Leflunomide: is a new oral agent in treatment of acute pancreatitis? Pancreas. 2010;39:237-42.
26. Sun Z, Zhao L, Wang H, Sun L, Yi H, Zhao Y. Presence of functional mouse regulatory CD4?CD25? T cells in xenogeneic neonatal porcine thymus-grafted athymic mice. Am J Transplant. 2006;6:2841-50.
27. Li XC, Rothstein DM, Sayegh MH. Costimulatory pathways in transplantation: challenges and new developments. Immunol Rev. 2009;229:271-93.
28. Giorgini A, Noble A. Blockade of chronic graft-versus-host disease by alloantigen-induced CD4?CD25?Foxp3? regulatory T cells in nonlymphopenic hosts. J Leukoc Biol. 2007;82:1053-61. (Pubitemid 350133501)
29. Velasquez-Lopera MM, Eaton VL, Lerret NM, Correa LA, Decresce RP, Garcia LF, Jaramillo A. Induction of transplantation tolerance by allogeneic donor-derived CD4(?)CD25(?)Foxp3(?) regulatory T cells. Transpl Immunol. 2008;19:127-35.
30. Edinger M. Regulatory T cells for the prevention of graft-versushost disease: professionals defeat amateurs. Eur J Immunol. 2009;39:2966-8.
31. Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, Del Papa B, Zei T, Ostini RI, Cecchini D, Aloisi T, Perruccio K, Ruggeri L, Balucani C, Pierini A, Sportoletti P, Aristei C, Falini B, Reisner Y, Velardi A, Aversa F, Martelli MF. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011;117:3921-8.
32. Bocian K, Borysowski J, Wierzbicki P, Wyzgal J, Klosowska D, Bialoszewska A, Paczek L, Gorski A, Korczak-Kowalska G. Rapamycin, unlike cyclosporine A, enhances suppressive functions of in vitro-induced CD4?CD25? Tregs. Nephrol Dial Transpl. 2010;25:710-7.
33. Francis RS, Feng G, Tha-In T, Lyons IS, Wood KJ, Bushell A. Induction of transplantation tolerance converts potential effector T cells into graft-protective regulatory T cells. Eur J Immunol. 2011;41:726-38.
34. Semple K, Yu Y, Wang D, Anasetti C, Yu XZ. Efficient and selective prevention of GVHD by antigen-specific induced Tregs via linked-suppression in mice. Biol Blood Marrow Transpl. 2011;17:309-18.
35. Kinsey GR, Sharma R, Huang L, Li L, Vergis AL, Ye H, Ju ST, Okusa MD. Regulatory T cells suppress innate immunity in kidney ischemia-reperfusion injury. J Am Soc Nephrol. 2009;20:1744-53.
36. Zhao Y. The different effects of cyclosporin A and rapamycin on regulatory CD4?CD25? T cells: potential relationship with transplant tolerance induction. Expert Rev Clin Immunol. 2007;3:245-9. (Pubitemid 46839299)
37. Friedman J, Weissman I. Two cytoplasmic candidates for immunophilin action are revealed by affinity for a new cyclophilin: one in the presence and one in the absence of CsA. Cell. 1991;66:799-806. (Pubitemid 121001713)
38. Tajima K, Amakawa R, Ito T, Miyaji M, Takebayashi M, Fukuhara S. Immunomodulatory effects of cyclosporin A on human peripheral blood dendritic cell subsets. Immunology. 2003;108:321-8. (Pubitemid 36332390)
39. Zeiser R, Nguyen VH, Beilhack A, Buess M, Schulz S, Baker J, Contag CH, Negrin RS. Inhibition of CD4?CD25? regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood. 2006;108:390-9. (Pubitemid 43990654)
40. Vincenti F, Jensik SC, Filo RS, Miller J, Pirsch J. A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years. Transplantation. 2002;73:775-82. (Pubitemid 34260577)
41. Wang H, Zhao L, Sun Z, Sun L, Zhang B, Zhao Y. A potential side effect of cyclosporin A: inhibition of CD4(?)CD25(?) regulatory T cells in mice. Transplantation. 2006;82:1484-92. (Pubitemid 44967632)
42. Antin JH, Kim HT, Cutler C, Ho VT, Lee SJ, Miklos DB, Hochberg EP, Wu CJ, Alyea EP, Soiffer RJ. Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation. Blood. 2003;102:1601-5. (Pubitemid 37022548)
43. Busca A, Locatelli F, Moscato D, Falda M. Sirolimus-related toxicity in stem cell transplantation. Biol Blood Marrow Transpl. 2005;11:647-9. (Pubitemid 41001640)
44. Breslin EM, White PC, Shore AM, Clement M, Brennan P. LY294002 and rapamycin co-operate to inhibit T-cell proliferation. Br J Pharmacol. 2005;144:791-800. (Pubitemid 40516119)
45. Qu Y, Zhang B, Zhao L, Liu G, Ma H, Rao E, Zeng C, Zhao Y. The effect of immunosuppressive drug rapamycin on regulatory CD4?CD25?Foxp3? T cells in mice. Transpl Immunol. 2007;17:153-61.
46. Wang TY, Li J, Li CY, Jin Y, Lu XW, Wang XH, Zhou Q. Leflunomide induces immunosuppression in collagen-induced arthritis rats by upregulating CD4?CD25? regulatory T cells. Can J Physiol Pharmacol. 2010;88:45-53.
47. Weigmann B, Jarman ER, Sudowe S, Bros M, Knop J, Reske- Kunz AB. Induction of regulatory T cells by leflunomide in a murine model of contact allergen sensitivity. J Invest Dermatol. 2006;126:1524-33.
48. Mrowka C, Thoenes GH, Langer KH, Bartlett RR. Prevention of the acute graft-versus-host disease (GVHD) in rats by the immunomodulating drug leflunomide. Ann Hematol. 1994;68: 195-9. (Pubitemid 24163529)