Marek's disease is a natural model for lymphomas overexpressing Hodgkin's disease antigen (CD30).

Animal models are essential for elucidating the molecular mechanisms of carcinogenesis. Hodgkin's and many diverse non-Hodgkin's lymphomas overexpress the Hodgkin's disease antigen CD30 (CD30(hi)), a tumor necrosis factor receptor II family member. Here we show that chicken Marek's disease (MD) lymphoma cells are also CD30(hi) and are a unique natural model for CD30(hi) lymphoma. Chicken CD30 resembles an ancestral form, and we identify a previously undescribed potential cytoplasmic signaling domain conserved in chicken, human, and mouse CD30. Our phylogeneic analysis defines a relationship between the structures of human and mouse CD30 and confirms that mouse CD30 represents the ancestral mammalian gene structure. CD30 expression by MD virus (MDV)-transformed lymphocytes correlates with expression of the MDV Meq putative oncogene (a c-Jun homologue) in vivo. The chicken CD30 promoter has 15 predicted high-stringency Meq-binding transcription factor recognition motifs, and Meq enhances transcription from the CD30 promoter in vitro. Plasma proteomics identified a soluble form of CD30. CD30 overexpression is evolutionarily conserved and defines one class of neoplastic transformation events, regardless of etiology. We propose that CD30 is a component of a critical intracellular signaling pathway perturbed in neoplastic transformation. Specific anti-CD30 Igs occurred after infection of genetically MD-resistant chickens with oncogenic MDV, suggesting immunity to CD30 could play a role in MD lymphoma regression.

[1]  Kanji Hirai,et al.  Marek’s Disease , 2001, Current Topics in Microbiology and Immunology.

[2]  E. Kieff,et al.  Tumor necrosis factor receptor associated factor 2 is a mediator of NF-kappa B activation by latent infection membrane protein 1, the Epstein-Barr virus transforming protein. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[3]  T. Werner,et al.  MatInd and MatInspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data. , 1995, Nucleic acids research.

[4]  G. Evan,et al.  Cancer‐A matter of life and cell death , 1997, International journal of cancer.

[5]  Toshiki Watanabe,et al.  Hodgkin’s Lymphoma and CD30 Signal Transduction , 2003, International journal of hematology.

[6]  S. Romagnani Biology of human TH1 and TH2 cells , 1995, Journal of Clinical Immunology.

[7]  Nancy F. Hansen,et al.  Comparative analyses of multi-species sequences from targeted genomic regions , 2003, Nature.

[8]  Toshiki Watanabe,et al.  CD30: expression and function in health and disease. , 1998, Seminars in immunology.

[9]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[10]  H. Skelton,et al.  A clonal cutaneous CD30+ lymphoproliferative eruption in a patient with evidence of past exposure to hepatitis E , 2000, International journal of dermatology.

[11]  S. Burgess,et al.  Resistance to Marek's Disease Herpesvirus-induced Lymphoma is Multiphasic and Dependent on Host Genotype , 2001, Veterinary pathology.

[12]  A. Houghton,et al.  Immunity against cancer: lessons learned from melanoma. , 2001, Current opinion in immunology.

[13]  T. Yoshino,et al.  Antisense oligodeoxynucleotides to latent membrane protein 1 induce growth inhibition, apoptosis and Bcl‐2 suppression in Epstein‐Barr virus (EBV)‐transformed B‐lymphoblastoid cells, but not in EBV‐positive natural killer cell lymphoma cells , 2001, British journal of haematology.

[14]  E. Coligan Current protocols in immunology , 1991 .

[15]  E. Podack,et al.  CD30—Governor of Memory T Cells? , 2002, Annals of the New York Academy of Sciences.

[16]  Y. Seko,et al.  Expression of tumour necrosis factor (TNF) ligand superfamily co‐stimulatory molecules CD30L, CD27L, OX40L, and 4‐1BBL in murine hearts with acute myocarditis caused by Coxsackievirus B3 , 2001, The Journal of pathology.

[17]  Shane C. Burgess,et al.  Identification of the Neoplastically Transformed Cells in Marek's Disease Herpesvirus-Induced Lymphomas: Recognition by the Monoclonal Antibody AV37 , 2002, Journal of Virology.

[18]  Titcomb Cp Non-Hodgkin's lymphoma: in a class all its own. , 2001 .

[19]  K. Schat,et al.  Syngeneic Marek's disease virus (MDV)-specific cell-mediated immune responses against immediate early, late, and unique MDV proteins. , 1996, Virology.

[20]  N. Meyers,et al.  H = W. , 1964, Proceedings of the National Academy of Sciences of the United States of America.

[21]  G. Inghirami,et al.  CD30 in normal and neoplastic cells. , 1999, Clinical immunology.

[22]  J. Lambert,et al.  CD30‐Positive Anaplastic Large Cell Lymphoma (ALCL) of T‐Cell Lineage in a 14‐Month‐Old Infant With Perinatally Acquired HIV‐1 Infection , 1998, Journal of pediatric hematology/oncology.

[23]  A. Krafft,et al.  Primary effusion lymphoma with herpesvirus 8 DNA in patients coinfected with HIV and hepatitis C virus: a report of 2 cases. , 2001, The AIDS reader.

[24]  Y. Sasaguri,et al.  Adult T-cell leukemia/lymphoma in which the pathohistological diagnosis was identical to that of Ki-1 positive anaplastic large cell lymphoma. , 1999, Internal medicine.

[25]  G. Pizzolo,et al.  Peripheral T lymphocyte cytokine profile (IFNgamma, IL-2, IL-4) and CD30 expression/release during measles infection. , 1999, Haematologica.

[26]  J. Panus,et al.  Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: A soluble, secreted CD30 homologue , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[27]  M. Sandberg,et al.  Characterization of LMP-1's association with TRAF1, TRAF2, and TRAF3 , 1997, Journal of virology.

[28]  R. Witter,et al.  Demonstration of a tumor-associated surface antigen in Marek's disease. , 1975, Journal of immunology.

[29]  Daniel Schumacher,et al.  Generation of a permanent cell line that supports efficient growth of Marek's disease virus (MDV) by constitutive expression of MDV glycoprotein E. , 2002, The Journal of general virology.

[30]  E. Kieff,et al.  Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[31]  H. Stein,et al.  Structure of the Hodgkin's lymphoma-associated human CD30 gene and the influence of a microsatellite region on its expression in CD30(+) cell lines. , 2001, Biochimica et biophysica acta.

[32]  L. Fugger,et al.  Spontaneous human squamous cell carcinomas are killed by a human cytotoxic T lymphocyte clone recognizing a wild-type p53-derived peptide. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[33]  P. Vandenabeele,et al.  TTRAP, a Novel Protein That Associates with CD40, Tumor Necrosis Factor (TNF) Receptor-75 and TNF Receptor-associated Factors (TRAFs), and That Inhibits Nuclear Factor-κB Activation* , 2000, The Journal of Biological Chemistry.

[34]  M. Tarkowski Expression and function of CD30 on T lymphocytes. , 1999, Archivum immunologiae et therapiae experimentalis.

[35]  Niels Grabe,et al.  AliBaba2: Context specific identification of transcription factor binding sites , 2000, Silico Biol..

[36]  A. Kutlar,et al.  Hb Hammersmith [β 42(CD1) Phe→Ser]: Occurrence as a De Novo Mutation in Black Monozygotic Twins With Multiple Congenital Anomalies , 1998 .

[37]  J. Young,et al.  A chicken homologue of the co-stimulating molecule CD80 which binds to mammalian CTLA-4 , 1999, Immunogenetics.

[38]  E. Kieff,et al.  Association of TRAF1, TRAF2, and TRAF3 with an Epstein-Barr virus LMP1 domain important for B-lymphocyte transformation: role in NF-kappaB activation , 1996, Molecular and cellular biology.

[39]  S. Burgess,et al.  Marek's disease virus EcoRI-Q gene (meq) and a small RNA antisense to ICP4 are abundantly expressed in CD4+ cells and cells carrying a novel lymphoid marker, AV37, in Marek's disease lymphomas. , 1997, The Journal of general virology.

[40]  A. Órfão,et al.  Optimal number of reagents required to evaluate hematolymphoid neoplasias: results of an international consensus meeting. , 2001, Cytometry.

[41]  K. Nazerian An updated list of avian cell lines and transplantable tumours. , 1987, Avian pathology : journal of the W.V.P.A.

[42]  M. Takeshita CD30-positive anaplastic large cell lymphoma with HTLV-I proviral integration: a unique histologic subgroup of adult T-cell leukemia/lymphoma. , 1999, Internal medicine.