Skip to main content
NCBI home page
Thorax logoLink to Thorax
. 1994 Feb;49(2):151–156. doi: 10.1136/thx.49.2.151

Development of immunological assays to monitor pulmonary allograft rejection.

A C Cunningham 1, J A Kirby 1, I W Colquhoun 1, P A Flecknell 1, T Ashcroft 1, J H Dark 1
PMCID: PMC474331  PMID: 8128405

Abstract

BACKGROUND--At present the diagnosis of pulmonary allograft rejection is made after examination of transbronchial biopsy specimens; this method is highly invasive. A study was performed to determine whether immunological parameters measured in peripheral blood or bronchoalveolar lavage samples correlate with the histological diagnosis of rejection. METHODS--Left unilateral pulmonary allotransplantation was performed between dogs. The animals were immunosuppressed with cyclosporin A after transplantation but the dose of this drug was gradually reduced to allow controlled rejection to take place. Rejection was diagnosed histologically. Four immunological parameters were investigated: measurement of lavage derived T cell proliferation in response to limited culture with interleukin 2; measurement of changes in the frequency of donor reactive cytotoxic T lymphocytes; assay of the level of donor cell binding IgG antibody in recipient plasma; and measurement of the antibody dependent cell mediated cytotoxic response to donor cells after labelling with recipient plasma. RESULTS--Assays based on measurement of the function of T cells produced significant results at a time later than the histological diagnosis of severe rejection. The level of donor reactive IgG antibody increased at a time that corresponded closely with the diagnosis of severe rejection. This IgG did not activate the antibody dependent cell mediated cytotoxic effector mechanism to a significant extent. CONCLUSIONS--Measurement of parameters of donor specific immunoreactivity can yield data which are indicative of severe pulmonary allograft rejection. These methods make use of samples which can be obtained by minimally invasive methods. Measurement of the plasma level of donor reactive IgG antibody appears to be the most useful assay. However, each of the in vitro assays used during this series of experiments was less sensitive to the onset of rejection than was routine histological examination.

Full text

PDF
151

Images in this article

153Image
on p.153

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berry G. J., Brunt E. M., Chamberlain D., Hruban R. H., Sibley R. K., Stewart S., Tazelaar H. D. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: Lung Rejection Study Group. The International Society for Heart Transplantation. J Heart Transplant. 1990 Nov-Dec;9(6):593–601. [PubMed] [Google Scholar]
  2. Bradley J. A., Mowat A. M., Bolton E. M. Processed MHC class I alloantigen as the stimulus for CD4+ T-cell dependent antibody-mediated graft rejection. Immunol Today. 1992 Nov;13(11):434–438. doi: 10.1016/0167-5699(92)90069-J. [DOI] [PubMed] [Google Scholar]
  3. Doveren R. F., Buurman W. A., van der Linden C. J., Strijbosch L. W., Spronken E. E., Kootstra G. Analysis of cytotoxic T lymphocyte response in rejecting allografted canine kidneys. Transplantation. 1986 Jan;41(1):33–38. doi: 10.1097/00007890-198601000-00006. [DOI] [PubMed] [Google Scholar]
  4. Herzog W. R., Zanker B., Irschick E., Huber C., Franz H. E., Wagner H., Kabelitz D. Selective reduction of donor-specific cytotoxic T lymphocyte precursors in patients with a well-functioning kidney allograft. Transplantation. 1987 Mar;43(3):384–389. doi: 10.1097/00007890-198703000-00013. [DOI] [PubMed] [Google Scholar]
  5. Higenbottam T. W., Whitehead B. Heart-lung transplantation for cystic fibrosis. J R Soc Med. 1991;84 (Suppl 18):18–21. [PMC free article] [PubMed] [Google Scholar]
  6. Higenbottam T., Stewart S., Penketh A., Wallwork J. Transbronchial lung biopsy for the diagnosis of rejection in heart-lung transplant patients. Transplantation. 1988 Oct;46(4):532–539. doi: 10.1097/00007890-198810000-00013. [DOI] [PubMed] [Google Scholar]
  7. Hooper T. L., Fetherston G. J., Flecknell P. A., Dark J. H., McGregor C. G. The use of a prostacyclin analog, iloprost, as an adjunct to pulmonary preservation with Euro-Collins solution. Transplantation. 1990 Mar;49(3):495–499. doi: 10.1097/00007890-199003000-00003. [DOI] [PubMed] [Google Scholar]
  8. Kirby J. A., Givan A. L., Shenton B. K., Talbot D., Forsythe J. L., Lennard T. W., Proud G., Taylor R. M. Renal allograft rejection. Possible involvement of antibody-dependent cell-mediated cytotoxicity. Transplantation. 1990 Aug;50(2):225–229. doi: 10.1097/00007890-199008000-00010. [DOI] [PubMed] [Google Scholar]
  9. Kirby J. A., Parfett G. J., Reader J. A., Pepper J. R. Lung transplantation in the rat: a model for study of the cellular mechanisms of allograft rejection. Immunology. 1988 Mar;63(3):369–372. [PMC free article] [PubMed] [Google Scholar]
  10. Kirby J. A., Pepper J. R., Reader J. A., Corbishley C. M., Hudson L. Precursor frequency of donor-specific lymphocytes recovered from canine lung transplants. Clin Exp Immunol. 1986 Feb;63(2):334–342. [PMC free article] [PubMed] [Google Scholar]
  11. Locke T. J., Hooper T. L., Flecknell P. A., McGregor C. G. Preservation of the lung. Comparison of topical cooling and cold crystalloid pulmonary perfusion. J Thorac Cardiovasc Surg. 1988 Nov;96(5):789–795. [PubMed] [Google Scholar]
  12. Miltenburg A. M., Meijer-Paape M. E., Weening J. J., Daha M. R., van Es L. A., van der Woude F. J. Induction of antibody-dependent cellular cytotoxicity against endothelial cells by renal transplantation. Transplantation. 1989 Oct;48(4):681–688. [PubMed] [Google Scholar]
  13. Mohanakumar T., Waldrep J. C., Phibbs M., Mendez-Picon G., Kaplan A. M., Lee H. M. Serological characterization of antibodies eluted from chronically rejected human renal allografts. Transplantation. 1981 Jul;32(1):61–66. doi: 10.1097/00007890-198107000-00013. [DOI] [PubMed] [Google Scholar]
  14. Norin A. J., Kamholz S. L. Evidence of intragraft interleukin-2-activated killer cells and allospecific cytolytic T lymphocytes in rejecting lung allografts. Transplantation. 1989 Nov;48(5):856–862. doi: 10.1097/00007890-198911000-00026. [DOI] [PubMed] [Google Scholar]
  15. Norin A. J., Kamholz S. L., Pinsker K. L., Emeson E. E., Veith F. J. Concanavalin A-dependent cell-mediated cytotoxicity in bronchoalveolar lavage fluid. Correlation with lung allograft rejection in mongrel dogs during cyclosporine dose tapering. Transplantation. 1986 Nov;42(5):466–472. [PubMed] [Google Scholar]
  16. Norin A. J. The immunobiology of experimental lung transplantation with cyclosporine immunosuppression: cytolytic T lymphocytes and delayed type hypersensitivity in rejecting and tolerant recipients. Transplant Proc. 1988 Apr;20(2 Suppl 2):125–130. [PubMed] [Google Scholar]
  17. Organ transplantation. Heart and lung. Transplant Proc. 1985 Feb;17(1 Pt 1):199–249. [PubMed] [Google Scholar]
  18. Rabinowich H., Zeevi A., Paradis I. L., Yousem S. A., Dauber J. H., Kormos R., Hardesty R. L., Griffith B. P., Duquesnoy R. J. Proliferative responses of bronchoalveolar lavage lymphocytes from heart-lung transplant patients. Transplantation. 1990 Jan;49(1):115–121. doi: 10.1097/00007890-199001000-00026. [DOI] [PubMed] [Google Scholar]
  19. Reader J. A., Burke M. M., Counihan P., Kirby J. A., Adams S., Davies M. J., Pepper J. R. Noninvasive monitoring of human cardiac allograft rejection. Transplantation. 1990 Jul;50(1):29–33. doi: 10.1097/00007890-199007000-00006. [DOI] [PubMed] [Google Scholar]
  20. Reitz B. A., Gaudiani V. A., Hunt S. A., Wallwork J., Billingham M. E., Oyer P. E., Baumgartner W. A., Jamieson S. W., Stinson E. B., Shumway N. E. Diagnosis and treatment of allograft rejection in heart-lung transplant recipients. J Thorac Cardiovasc Surg. 1983 Mar;85(3):354–361. [PubMed] [Google Scholar]
  21. Schon-Hegrad M. A., Oliver J., McMenamin P. G., Holt P. G. Studies on the density, distribution, and surface phenotype of intraepithelial class II major histocompatibility complex antigen (Ia)-bearing dendritic cells (DC) in the conducting airways. J Exp Med. 1991 Jun 1;173(6):1345–1356. doi: 10.1084/jem.173.6.1345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Shennib H., Nguyen D. Bronchoalveolar lavage in lung transplantation. Ann Thorac Surg. 1991 Feb;51(2):335–340. doi: 10.1016/0003-4975(91)90824-a. [DOI] [PubMed] [Google Scholar]
  23. Westra A. L., Prop J., Kuijpers K. C., Wildevuur C. R. A paradox in heart and lung rejection. Transplantation. 1990 Apr;49(4):826–828. [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES