Experimental Hematology
Volume 35, Issue 4 , Pages 596-604 , April 2007

The relationships between Epstein-Barr virus latent membrane protein 1 and regulatory T cells in Hodgkin's lymphoma

  • Neil A. Marshall

      Affiliations

    • Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK
    • Corresponding Author InformationOffprint requests to: Neil A Marshall, Ph.D., Research Fellow, Department of Medicine and Therapeutics, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK
  • ,
  • Dominic J. Culligan

      Affiliations

    • Department of Haematology, University of Aberdeen, Aberdeen, UK
  • ,
  • Jane Tighe

      Affiliations

    • Department of Haematology, University of Aberdeen, Aberdeen, UK
  • ,
  • Peter W. Johnston

      Affiliations

    • Department of Pathology, University of Aberdeen, Aberdeen, UK
  • ,
  • Robert N. Barker

      Affiliations

    • Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK
  • ,
  • Mark A. Vickers

      Affiliations

    • Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK

Received 13 September 2006 ,Revised 23 December 2006 ,Accepted 12 January 2007.

References 

  1. Niedobitek G, Meru N, Delecluse HJ. Epstein-Barr virus infection and human malignancies. Int J Exp Pathol. 2001;82:149–170
  2. Herbst H. Epstein-Barr virus in Hodgkin's disease. Semin Cancer Biol. 1996;7:183–189
  3. Weiss LM, Strickler JG, Warnke RA, Purtilo DT, Sklar J. Epstein-Barr viral DNA in tissues of Hodgkin's disease. Am J Pathol. 1987;129:86–91
  4. Pallesen G, Hamilton-Dutoit SJ, Rowe M, Young LS. Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease. Lancet. 1991;337:320–322
  5. Hjalgrim H, Askling J, Rostgaard K, Hamilton-Dutoit S, Frisch M, Zhang JS, et al. Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Engl J Med. 2003;349:1324–1332
  6. Jarrett RF. Risk factors for Hodgkin's lymphoma by EBV status and significance of detection of EBV genomes in serum of patients with EBV-associated Hodgkin's lymphoma. Leuk Lymphoma. 2003;44(Suppl 3):S27–S32
  7. Kieff E, Rickinson AB. Epstein-Barr virus and its replication. In:  Knipe DM,  Howley PM editor. Fundamental virology. 4th ed.. Philadelphia: Lippincott-Raven; 2001;p. 2511–2573
  8. Deacon EM, Pallesen G, Niedobitek G, Crocker J, Brooks L, Rickinson AB, et al. Epstein-Barr virus and Hodgkin's disease: Transcriptional analysis of virus latency in the malignant cells. J Exp Med. 1993;177:339–349
  9. Grasser FA, Murray PG, Kremmer E, Klein K, Rembeger K, Feiden W, et al. Monoclonal antibodies directed against the Epstein-Barr virus-encoded nuclear antigen 1 (EBNA-1): immunohistologic detection of EBNA-1 in the malignant cells of Hodgkin's disease. Blood. 1994;84:3792–3798
  10. Niedobitek G, Kremmer E, Herbst H, Whitehead L, Dawson CW, Niedobitek E, et al. Immunohistochemical detection of the Epstein-Barr virus-encoded latent membrane protein 2A and Hodgkin's disease and infectious mononucleosis. Blood. 1997;90:1664–1672
  11. Herbst H, Dallenbach F, Hummel M, Hiedobitek G, Rileri S, Muller-Lantzch N, et al. Epstein-Barr virus latent membrane protein expression in Hodgkin and Reed-Sternberg cells. Proc Natl Acad Sci U S A. 1991;88:4766–4770
  12. Straathof KC, Savoldo B, Heslop HE, Rooney CM. Immunotherapy for post-transplant lymphoproliferative disease. Br J Haematol. 2002;118:728–740
  13. Huls MH, Rooney CM, Heslop HE. Adoptive T-cell therapy for Epstein-Barr virus-positive Hodgkin's disease. Acta Haematol. 2003;110:149–153
  14. Bollard CM, Savoldo B, Rooney CM, Heslop HE. Adoptive T-cell therapy for EBV-associated post-transplant lymphoproliferative disease. Acta Haematol. 2003;110:139–148
  15. Bollard CM, Straathof KC, Huls MH, Leen A, Lacuesta K, Davis A, et al. The generation and characterization of LMP2-specific CTLs for use as adoptive transfer from patients with relapsed EBV-positive Hodgkin disease. J Immunother. 2004;27:317–327
  16. Bollard CM, Kuehnle I, Leen A, Rooney CM, Heslop HE. Adoptive immunotherapy for posttransplantation viral infections. Biol Blood Marrow Transplant. 2004;10:143–155
  17. Haque T, Wilkie GM, Taylor C, Amlot PL, Murad P, Iley A, et al. Treatment of Epstein-Barr-virus-positive post-transplantation lymphoproliferative disease with partly HLA-matched allogeneic cytotoxic T cells. Lancet. 2002;360:436–442
  18. Janssen EM, Lemmens EE, Wolfe T, Christen U, von Herrath MG, Schoenberger SP. CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes. Nature. 2003;421:852–856
  19. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986;136:2348–2357
  20. Kronenberg M, Rudensky A. Regulation of immunity by self-reactive T cells. Nature. 2005;435:598–604
  21. Hauben E, Roncarolo MG. Human CD4+ regulatory T cells and activation-induced tolerance. Microbes Infect. 2005;7:1023–1032
  22. MacDonald AJ, Duffy M, Brady MT, McKiernan S, Hall W, Hegarty J, et al. CD4 helper type 1 and regulatory T cells induced against the same epitopes on the core protein in hepatitis C virus-infected persons. J Infect Dis. 2002;185:720–727
  23. Marshall NA, Vickers MA, Barker RN. Regulatory T cells secreting IL-10 dominate the immune response to EBV latent membrane protein 1. J Immunol. 2003;170:6183–6189
  24. Wang HY, Wang RF. Antigen-specific CD4+ regulatory T cells in cancer: implications for immunotherapy. Microbes Infect. 2005;7:1056–1062
  25. Liyanage UK, Moore TT, Joo HG, Tanaka Y, Herrmann V, Doherty G, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol. 2002;169:2756–2761
  26. Levings MK, Roncarolo MG. T-regulatory 1 cells: a novel subset of CD4 T cells with immunoregulatory properties. J Allergy Clin Immunol. 2000;106:S109–S112
  27. Weiner HL. Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol Rev. 2001;182:207–214
  28. Piccirillo CA, Letterio JJ, Thornton AM, McHugh RS, Mamura M, Mizuhara H, et al. CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness. J Exp Med. 2002;196:237–246
  29. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057–1061
  30. Murray RJ, Kurilla MG, Brooks JM, Thomas WA, Rowe M, Kieff E, et al. Identification of target antigens for the human cytotoxic T cell response to EBV: implications for the immune control of EBV+ malignancies. J Exp Med. 1992;176:157–168
  31. Khanna R, Burrows SR, Nicholls J, Poulsen LM. Identification of cytotoxic T cell epitopes within Epstein-Barr virus (EBV) oncogene latent membrane protein 1 (LMP1): evidence for HLA A2 supertype-restricted immune recognition of EBV-infected cells by LMP1-specific cytotoxic T lymphocytes. Eur J Immunol. 1998;28:451–458
  32. Leen A, Meij P, Redchenko I, Middeldorp J, Bloemena E, Rickinson A, et al. Differential immunogenicity of Epstein-Barr virus latent-cycle proteins for human CD4(+) T-helper 1 responses. J Virol. 2001;75:8649–8659
  33. Chapman ALN, Rickinson AB, Thomas WA, Jarrett RF, Crocker J, Lee SP. Epstein-Barr Virus-specific cytotoxic T lymphocyte responses in the blood and tumour site of Hodgkin's disease patients: implications for a T-cell-based therapy. Cancer Res. 2001;61:6219–6226
  34. Marshall NA, Christie LE, Munro LR, Culligan DJ, Johnston PW, Barker RN, et al. Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood. 2004;103:1755–1762
  35. Plebanski M, Saunders M, Burtles SS, Crowe S, Hooper DC. Primary and secondary human in vitro T-cell responses to soluble antigens are mediated by subsets bearing different CD45 isoforms. Immunology. 2002;75:86–91
  36. Baer R, Bankier AT, Biggin MD, Deininger PL, Farrell PJ, Gibson TJ, et al. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984;310:207–211
  37. Stott LM, Barker RN, Urbaniak SJ. Identification of alloreactive T-cell epitopes on the Rhesus D protein. Blood. 2000;96:4011–4019
  38. Devereux G, Hall AM, Barker RN. Measurement of T-helper cytokines secreted by cord blood mononuclear cells in response to allergens. J Immunol Methods. 2000;234:13–22
  39. Dukers DF, Jaspars LH, Vos W, Oudejans JJ, Hayes D, Cillessen S, et al. Quantitative immunohistochemical analysis of cytokine profiles in Epstein-Barr virus-positive and -negative cases of Hodgkin's disease. J Pathol. 2000;190:143–149
  40. Levy R, Kaplan HS. Impaired lymphocyte function in untreated Hodgkin's disease. N Engl J Med. 1974;290:181–186
  41. Schulof RS, Bockman RS, Garofalo JA, Cirrincione C, Cunningham-Rundles S, Fernandes G, et al. Multivariate analysis of T-cell functional defects and circulating serum factors in Hodgkin's disease. Cancer. 1981;48:964–973
  42. Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, et al. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med. 1995;333:1038–1044
  43. Oudejans JJ, Jiwa NM, Kummer JA, Ossenkoppele GJ, van Heerde P, Baars JW, et al. Activated cytotoxic T cells as prognostic marker in Hodgkin's disease. Blood. 1997;89:1376–1382
  44. Alvaro T, Lejeune M, Salvado MT, Bosch R, Garcia JF, Jaen J, et al. Outcome in Hodgkin's lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells. Clin Cancer Res. 2005;11:1467–1473
  45. Gottschalk S, Edwards OL, Sili U, Huls MH, Goltsova T, Davis AR, et al. Generating CTLs against the subdominant Epstein-Barr virus LMP1 antigen for the adoptive immunotherapy of EBV-associated malignancies. Blood. 2003;101:1905–1912

PII: S0301-472X(07)00033-1

doi: 10.1016/j.exphem.2007.01.030

Experimental Hematology
Volume 35, Issue 4 , Pages 596-604 , April 2007