1887

Abstract

Post-transplant lymphoproliferative disease (PTLD) biopsy material is rarely available in adequate quantity for research. Therefore, the present study was designed to expand biopsy material in scid mice. Epstein–Barr virus (EBV)+ve PTLD samples from five transplant patients were established in scid mice. PCR analysis of immunoglobulin gene rearrangements demonstrated that four of the five biopsies (80%) gave rise to scid tumours which represented the original tumour cell clones. Immunophenotyping showed that these four biopsies (and all scid tumours) expressed all EBV latent genes and a B lymphoblast phenotype; ≤26% T cells were found in the biopsy material whereas scid tumours showed a paucity of T lymphocytes. RT–PCR analysis revealed expression of IL-2, -4, -6, -10 and IFN-γ in all tumour material, suggesting key roles for these factors in tumour growth. The results show that EBV+ve PTLD material can be expanded in scid mice giving rise to quantities of homogeneous malignant tissue sufficient for research studies.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-1-173
2002-01-01
2020-08-05
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/1/0830173a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-1-173&mimeType=html&fmt=ahah

References

  1. Armitage J. M., Kormos R. L., Stuart R. S., Fricker F. J., Griffith B. P., Nalesnik M., Hardesty R. L., Dummer J. S.. 1991; Posttransplant lymphoproliferative disease in thoracic organ transplant patients: ten years of cyclosporine-based immunosuppression. Journal of Heart and Lung Transplantation10:877–886
    [Google Scholar]
  2. Bosma G. C., Custer R. P., Bosma M. J.. 1983; A severe combined immunodeficiency mutation in the mouse. Nature301:527–530
    [Google Scholar]
  3. Cen H., Williams P. A., McWilliams H. P., Breinig M. C., Ho M., McKnight J. L. C.. 1993; Evidence for restricted Epstein–Barr virus latent gene expression and anti-EBNA antibody response in solid organ transplant recipients with posttransplant lymphoproliferative disorders. Blood81:1393–1403
    [Google Scholar]
  4. Crawford D. H.. 2001; Biology and disease associations of Epstein–Barr virus. Philosophical Transactions of the Royal Society of London B Biological Sciences356:461–473
    [Google Scholar]
  5. Deacon E. M., Pallesen G., Niedobitek G., Crocker J., Brooks L., Rickinson A. B., Young L. S.. 1993; Epstein–Barr virus and Hodgkin′s disease: transcriptional analysis of virus latency in the malignant cells. Journal of Experimental Medicine177:339–349
    [Google Scholar]
  6. Gardella T., Medveczky P., Sairenji T., Mulder C.. 1984; Detection of circular and linear herpesvirus DNA molecules in mammalian cells by electrophoresis. Journal of Virology50:248–254
    [Google Scholar]
  7. Ho M., Miller G., Atchison R. W., Breinig M. K., Dummer J. S., Andiman W., Starzl T. E., Eastman R., Griffith B. P., Hardesty R. L.. 1985; Epstein–Barr virus infections and DNA hybridization studies in posttransplantation lymphoma and lymphoproliferative lesions: the role of primary infection. Journal of Infectious Diseases152:876–886
    [Google Scholar]
  8. Howe J. G., Steitz J. A.. 1986; Localization of Epstein–Barr virus-encoded small RNAs by in situ hybridization. Proceedings of the National Academy of Sciences, USA83:9006–9010
    [Google Scholar]
  9. Hurley E. A., Thorley-Lawson D. A.. 1988; B cell activation and the establishment of Epstein–Barr virus latency. Journal of Experimental Medicine168:2059–2075
    [Google Scholar]
  10. Itoh T., Shiota M., Takanashi M., Hojo I., Satoh H., Matsuzawa A., Moriyama T., Watanabe T., Hirai K., Mori S.. 1993; Engraftment of human non-Hodgkin lymphomas in mice with severe combined immunodeficiency. Cancer72:2686–2694
    [Google Scholar]
  11. Johannessen I., Crawford D. H.. 1999; In vivo models for Epstein–Barr virus (EBV)-associated B cell lymphoproliferative disease (BLPD. Reviews in Medical Virology9:263–277
    [Google Scholar]
  12. Johannessen I., Asghar M., Crawford D. H.. 2000; Essential role for T cells in human B cell lymphoproliferative disease development in SCID mice. British Journal of Haematology109:600–610
    [Google Scholar]
  13. Kuppers R., Hansmann M.-L., Rajewsky K.. 1995; Micromanipulation and PCR analysis of single cells from tissue sections. In Handbook of Experimental Immunology pp. 206, 1–4 Edited by Weir D. M., Blackwell C., Herzenberg L. A.. Cambridge, MA: Blackwell Scientific;
    [Google Scholar]
  14. McCarthy K., Sloane J., Wiedermann L.. 1990; Rapid method for distinguishing clonal from polyclonal B cell populations in surgical biopsy specimens. Journal of Clinical Pathology43:429–432
    [Google Scholar]
  15. Meggetto F., Muller C., Henry S., Selves J., Mariame B., Brousset P., Saati T. A., Delsol G.. 1996; Epstein–Barr virus (EBV)-associated lymphoproliferations in severe combined immunodeficient mice transplanted with Hodgkin′s disease lymph nodes: implication of EBV+ve bystander B lymphocytes rather than EBV-infected Reed–Sternberg cells. Blood87:2435–2442
    [Google Scholar]
  16. Opelz G., Henderson R.. 1993; Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients. Lancet342:1514–1516
    [Google Scholar]
  17. Oudejans J. J., Jiwa M., van den Brule A. J., Grasser F. A., Horstman A., Vos W., Kluin P. M., van der Valk P., Walboomers J. M., Meijer C. J.. 1995; Detection of heterogeneous Epstein–Barr virus gene expression patterns within individual post-transplantation lymphoproliferative disorders. American Journal of Pathology147:923–933
    [Google Scholar]
  18. Perera S. M., Johannessen I., Thomas J. A., Brooks L. A., Jobe J. N., Crawford D. H., Radley-Smith R., Phillips M.. 1996; Growth of Epstein–Barr virus-associated B-lymphoproliferative disease tissue in a severe combined immunodeficient mouse. Blood88:1123–1125
    [Google Scholar]
  19. Perera S. M., Thomas J. A., Burke M., Crawford D. H.. 1998; Analysis of the T-cell micro-environment in Epstein–Barr virus-related post-transplantation B lymphoproliferative disease. Journal of Pathology184:177–184
    [Google Scholar]
  20. Raab-Traub N., Flynn K.. 1986; The structure of the termini of the Epstein–Barr virus as a marker of clonal cellular proliferation. Cell47:883–889
    [Google Scholar]
  21. Randhawa P. S., Pietrzak B., Nalesnik M. A., Demetris A. J., Locker J.. 1997; Subcutaneous implantation of human post-transplant lymphoproliferative disease lesions in scid mice. Hematological Oncology15:39–46
    [Google Scholar]
  22. Reedman B. M., Klein G.. 1973; Cellular localization of an Epstein–Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. International Journal of Cancer11:499–520
    [Google Scholar]
  23. Rubini J. R., Cronkite E. P., Bond V. P., Fliedner T. M.. 1960; The metabolism and fate of tritiated thymidine in man. Journal of Clinical Investigation39:909–918
    [Google Scholar]
  24. Stetler-Stevenson M., Crush-Stanton S., Cossman J.. 1990; Involvement of the bcl-2 gene in Hodgkin′s disease. Journal of the National Cancer Institute82:855–858
    [Google Scholar]
  25. Taylor J. H., Woods P. S., Hughes W. L.. 1957; The organization and duplication of chromosomes as revealed by autoradiographic studies using tritium-labeled thymidine. Proceedings of the National Academy of Sciences, USA43:122–128
    [Google Scholar]
  26. Thomas J. A., Hotchin N. A., Allday M. J., Amlot P., Rose M., Yacoub M., Crawford D. H.. 1990; Immunohistology of Epstein–Barr virus-associated antigens in B cell disorders from immunocompromised individuals. Transplantation49:944–953
    [Google Scholar]
  27. Van Noorden S.. 1986; Tissue preparation and immunostaining techniques for light microscopy. In Immunocytochemistry: Modern Methods and Applications pp26–53 Edited by Polak J. M., Van Noorden S.. Bristol: Wright;
    [Google Scholar]
  28. Yamamura M., Uyemura K., Deans R. J., Weinberg K., Rea T. H., Bloom B. R., Modlin R. L.. 1991; Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science254:277–279
    [Google Scholar]
  29. Yamamura M., Wang X. H., Ohmen J. D., Uyemura K., Rea T. H., Bloom B. R., Modlin R. L.. 1992; Cytokine patterns of immunologically mediated tissue damage. Journal of Immunology149:1470–1475
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-1-173
Loading
/content/journal/jgv/10.1099/0022-1317-83-1-173
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error