Intrahepatic regulatory T cells in autoimmune hepatitis are associated with treatment response and depleted with current therapies

Journal of Hepatology

Volumn 61, Issue 5, 2014, Pages 1106-1114

  Taubert, Richard ^a   Hardtke Wolenski, Matthias ^a   Noyan, Fatih ^a   Wilms, Artur ^a   Baumann, Anna K ^a   Schlue, Jerome ^a   Olek, Sven ^b   Falk, Christine S ^a   Manns, Michael P ^a   Jaeckel, Elmar ^a  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b EPIONTIS GMBH   (Germany)

Author keywords

Azathioprine; B cells; FOXP3; Hypergammaglobulinemia; IgG; Liver infiltrating lymphocyte; Prednisolone; Remission; Therapy

Indexed keywords

AZATHIOPRINE; BUDESONIDE; FORMALDEHYDE; IMMUNOGLOBULIN G; MYCOPHENOLATE MOFETIL; PARAFFIN; PREDNISOLONE; STEROID; TRANSCRIPTION FACTOR FOXP3;

ADAPTIVE IMMUNITY; ADULT; ARTICLE; AUTOIMMUNE HEPATITIS; B LYMPHOCYTE; CD4 CD8 RATIO; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE ACTIVITY; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOFLUORESCENCE; IMMUNOGLOBULIN BLOOD LEVEL; IMMUNOPHENOTYPING; IMMUNOSUPPRESSIVE TREATMENT; LIVER BIOPSY; LYMPHOCYTE DEPLETION; MALE; PHENOTYPE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REMISSION; T CELL DEPLETION; T LYMPHOCYTE; TREATMENT RESPONSE; ADVERSE EFFECTS; AGED; BIOSYNTHESIS; BLOOD; HEPATITIS, AUTOIMMUNE; IMMUNOLOGY; LIVER; MIDDLE AGED; PATHOLOGY; PROCEDURES; RECURRENT DISEASE; RETROSPECTIVE STUDY; T LYMPHOCYTE SUBPOPULATION;

ADAPTIVE IMMUNITY; ADULT; AGED; B-LYMPHOCYTES; FEMALE; HEPATITIS, AUTOIMMUNE; HUMANS; IMMUNOGLOBULIN G; IMMUNOPHENOTYPING; IMMUNOSUPPRESSION; LIVER; MALE; MIDDLE AGED; RECURRENCE; RETROSPECTIVE STUDIES; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY;

EID: 84932110028     PISSN: 01688278     EISSN: 16000641     Source Type: Journal    
DOI: 10.1016/j.jhep.2014.05.034     Document Type: Article

References (41)

1. Czaja AJ, Manns MP. Advances in the diagnosis, pathogenesis, and management of autoimmune hepatitis. Gastroenterology 2010;139: E54.
2. + T cells. Hepatology 2013;58(2): 718-728.
3. van der Vliet HJ, Nieuwenhuis EE. IPEX as a result of mutations in FOXP3. Clin Dev Immunol 2007;2007: 89017.
4. Buckner JH. Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol 2010;10: 849-859.
5. Longhi MS, Ma Y, Bogdanos DP, Cheeseman P, Mieli-Vergani G, Vergani D. Impairment of CD4(+)CD25(+) regulatory T-cells in autoimmune liver disease. J Hepatol 2004;41: 31-37.
6. + CD25+ regulatory T-cells on CD8 T-cell function in patients with autoimmune hepatitis. J Autoimmun 2005;25: 63-71.
7. +CD25+ regulatory T cells in health and autoimmune hepatitis. J Immunol 2006;176: 4484-4491.
8. Ferri S, Longhi MS, De Molo C, Lalanne C, Muratori P, Granito A, et al. A multifaceted imbalance of T cells with regulatory function characterizes type 1 autoimmune hepatitis. Hepatology 2010;52: 999-1007.
9. Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 2010;10: 490-500.
10. + T cells expressing the FoxP3 transcription factor. Immunity 2009;30: 899-911.
11. Baron U, Floess S, Wieczorek G, Baumann K, Grutzkau A, Dong J, et al. DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3(+) conventional T cells. Eur J Immunol 2007;37: 2378-2389.
12. Peiseler M, Sebode M, Franke B, Wortmann F, Schwinge D, Quaas A, et al. FOXP3+ regulatory T cells in autoimmune hepatitis are fully functional and not reduced in frequency. J Hepatol 2012;57(1): 125-132.
13. Longhi MS, Ma Y, Grant CR, Samyn M, Gordon P, Mieli-Vergani G, et al. T-regs in autoimmune hepatitis-systemic lupus erythematosus/mixed connective tissue disease overlap syndrome are functionally defective and display a Th1 cytokine profile. J Autoimmun 2013;41: 146-151.
14. Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, et al. International Autoimmune Hepatitis Group Report: Review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999;31: 929-938.
15. Taubert R, Pischke S, Schlue J, Wedemeyer H, Noyan F, Heim A, et al. Enrichment of regulatory T cells in acutely rejected human liver allografts. Am J Transplant 2012;12: 3425-3436.
16. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995;22: 696-699.
17. Bohne F, Martinez-Llordella M, Lozano JJ, Miquel R, Benitez C, Londono MC, et al. Intra-graft expression of genes involved in iron homeostasis predicts the development of operational tolerance in human liver transplantation. J Clin Invest 2012;122: 368-382.
18. Gavin MA, Torgerson TR, Houston E, DeRoos P, Ho WY, Stray-Pedersen A, et al. Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc Natl Acad Sci U S A 2006;103: 6659-6664.
19. Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, et al. Diagnosis and management of autoimmune hepatitis. Hepatology 2010;51: 2193-2213.
20. Oo YH, Weston CJ, Lalor PF, Curbishley SM, Withers DR, Reynolds GM, et al. Distinct roles for CCR4 and CXCR3 in the recruitment and positioning of regulatory T cells in the inflamed human liver. J Immunol 2010;184: 2886-2898.
21. Sakaki M, Hiroishi K, Baba T, Ito T, Hirayama Y, Saito K, et al. Intrahepatic status of regulatory T cells in autoimmune liver diseases and chronic viral hepatitis. Hepatol Res 2008;38: 354-361.
22. Lan RY, Cheng C, Lian ZX, Tsuneyama K, Yang GX, Moritoki Y, et al. Livertargeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis. Hepatology 2006;43: 729-737.
23. Taflin C, Miyara M, Nochy D, Valeyre D, Naccache JM, Altare F, et al. FoxP3+ regulatory T cells suppress early stages of granuloma formation but have little impact on sarcoidosis lesions. Am J Pathol 2009;174: 497-508.
24. Wieczorek G, Asemissen A, Model F, Turbachova I, Floess S, Liebenberg V, et al. Quantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissue. Cancer Res 2009;69: 599-608.
25. Knolle PA, Thimme R. Hepatic immune regulation and its involvement in viral hepatitis infection. Gastroenterology 2014;146(5): 1193-1207.
26. Santodomingo-Garzon T, Han J, Le T, Yang Y, Swain MG. Natural killer T cells regulate the homing of chemokine CXC receptor 3-positive regulatory T cells to the liver in mice. Hepatology 2009;49: 1267-1276.
27. Marelli-Berg FM, Clement M, Mauro C, Caligiuri G. An immunologist's guide to CD31 function in T-cells. J Cell Sci 2013;126: 2343-2352.
28. Fornasa G, Clement M, Groyer E, Gaston AT, Khallou-Laschet J, Morvan M, et al. A CD31-derived peptide prevents angiotensin II-induced atherosclerosis progression and aneurysm formation. Cardiovasc Res 2012;94: 30-37.
29. Lettmann KA, Hardtke-Wolenski M. The importance of liver microcirculation in promoting autoimmune hepatitis via maintaining an inflammatory cytokine milieu -A mathematical model study. J Theor Biol 2014;348C: 33-46.
30. Miyao T, Floess S, Setoguchi R, Luche H, Fehling HJ, Waldmann H, et al. Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells. Immunity 2012;36: 262-275.
31. Holder BS, Grant CR, Liberal R, Ma Y, Heneghan MA, Mieli-Vergani G, et al. Retinoic acid stabilizes antigen-specific regulatory T-cell function in autoimmune hepatitis type 2. J Autoimmun 2014, [Epub ahead of print].
32. Mallone R, Mannering SI, Brooks-Worrell BM, Durinovic-Bello I, Cilio CM, Wong FS, et al. Isolation and preservation of peripheral blood mononuclear cells for analysis of islet antigen-reactive T cell responses: Position statement of the T-Cell Workshop Committee of the Immunology of Diabetes Society. Clin Exp Immunol 2011;163: 33-49.
33. Grant CR, Liberal R, Holder BS, Cardone J, Ma Y, Robson SC, et al. Dysfunctional CD39(POS) regulatory T cells and aberrant control of T-helper type 17 cells in autoimmune hepatitis. Hepatology 2014;59: 1007-1015.
34. Liberal R, Grant CR, Holder BS, Ma Y, Mieli-Vergani G, Vergani D, et al. The impaired immune regulation of autoimmune hepatitis is linked to a defective galectin-9/tim-3 pathway. Hepatology 2012;56: 677-686.
35. Issa F, Hester J, Milward K, Wood KJ. Homing of regulatory T cells to human skin is important for the prevention of alloimmune-mediated pathology in an in vivo cellular therapy model. PLoS One 2012;7: E53331.
36. Saeki C, Nakano M, Takahashi H, Saito S, Homma S, Tajiri H, et al. Accumulation of functional regulatory T cells in actively inflamed liver in mouse dendritic cell-based autoimmune hepatic inflammation. Clin Immunol 2010;135: 156-166.
37. Chen X, Oppenheim JJ, Winkler-Pickett RT, Ortaldo JR, Howard OM. Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3(+)CD4(+)CD25(+) T regulatory cells in vivo and enhances their capacity to suppress EAE. Eur J Immunol 2006;36: 2139-2149.
38. + CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo. J Clin Invest 2006;116: 2423-2433.
39. Lapierre P, Beland K, Yang R, Alvarez F. Adoptive transfer of ex vivo expanded regulatory T cells in an autoimmune hepatitis murine model restores peripheral tolerance. Hepatology 2013;57: 217-227.
40. Maruoka R, Aoki N, Kido M, Iwamoto S, Nishiura H, Ikeda A, et al. Splenectomy prolongs the effects of corticosteroids in mouse models of autoimmune hepatitis. Gastroenterology 2013;145(1): 209-220.
41. Marceau G, Yang R, Lapierre P, Beland K, Alvarez F. Low-dose anti-CD3 antibody induces remission of active autoimmune hepatitis in xenoimmunized mice. Liver Int 2014, [Epub ahead of print].