Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 Oct;98(1):158–162. doi: 10.1111/j.1365-2249.1994.tb06623.x

The development of transplant coronary artery disease after cardiac transplantation is correlated with a predominance of CD8+ T lymphocytes in endomyocardial biopsy derived T cell cultures.

N H Jutte 1, K Groeneveld 1, A H Balk 1, A J Ouwehand 1, E H Loonen 1, M Van der Linden 1, S Strikwerda 1, B Mochtar 1, F H Claas 1, W Weimar 1
PMCID: PMC1534186  PMID: 7923876

Abstract

Long-term survival of heart transplant recipients is limited by the development of transplant coronary artery disease (TCAD). We analysed whether the development of TCAD is correlated with the incidence of acute rejection episodes, with the formation of anti-HLA antibodies or with the composition and function of T lymphocyte cultures derived from endomyocardial biopsies. TCAD was assessed by visual analysis of annually performed coronary angiograms and defined as the presence of all vascular changes, including minor wall irregularities. One year after transplantation, 31 of the 77 patients studied had TCAD (40%). The median age and mean number of HLA mismatches in patients with or without TCAD were highly comparable. The patient groups did not differ in incidence of acute rejection episodes, nor in percentage of endomyocardial biopsies yielding T cell cultures. At 1 year after transplantation, lymphocyte cultures from 18/31 TCAD+ patients (58%) and 27/46 TCAD- patients (57%) were analysed. The TCAD+ patients had, compared with the TCAD- patients, a higher median percentage of CD8+ T cells (71% versus 25%, P = 0.06) and a lower median percentage of CD4+ T cells (4% versus 40%, P = 0.04). Similar differences were found in a longitudinal analysis of the culture results of endomyocardial biopsies (EMBs) obtained during the first year. The cytotoxic reactivity of the cultures against donor HLA class I or class II antigens was comparable in the two groups, although a difference in recognition of heart specific antigens remains possible. The fact that EMB-derived cultures from TCAD+ and TCAD- patients differed in T cell phenotype populations gives some support to the hypothesis that cellular immunological processes are involved in the development of TCAD. However, while the median values differed, the overlap of the percentages of CD8+ cells in cultures from TCAD- and TCAD+ patients shows that other factors besides CD8+ T cells also play a role.

Full text

PDF
158

Selected References

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

  1. Ahmed-Ansari A., Tadros T., Dempsey C. L., Knopf W. D., Leatherbury A., Gravanis M. B., Murphy D. A., Goodroe J. H., Sell K. W. Characterization of human cardiac infiltrating cells post transplantation. 1. Phenotypic and functional alloreactivity. Am J Cardiovasc Pathol. 1988;2(3):193–210. [PubMed] [Google Scholar]
  2. Balk A. H., Simoons M. L., vd Linden M. J., de Feyter P. J., Mochtar B., Weimar W., Bos E. Coronary artery disease after heart transplantation: timing of coronary arteriography. J Heart Lung Transplant. 1993 Jan-Feb;12(1 Pt 1):89–99. [PubMed] [Google Scholar]
  3. Barbir M., Banner N., Thompson G. R., Khaghani A., Mitchell A., Yacoub M. Relationship of immunosuppression and serum lipids to the development of coronary arterial disease in the transplanted heart. Int J Cardiol. 1991 Jul;32(1):51–56. doi: 10.1016/0167-5273(91)90043-o. [DOI] [PubMed] [Google Scholar]
  4. Bender J. R., Pardi R., Kosek J., Engleman E. G. Evidence that cytotoxic lymphocytes alter and traverse allogeneic endothelial cell monolayers. Transplantation. 1989 Jun;47(6):1047–1053. doi: 10.1097/00007890-198906000-00026. [DOI] [PubMed] [Google Scholar]
  5. Bruning J. W., Claas F. H., Kardol M. J., Lansbergen Q., Naipal A. M., Tanke H. J. Automated reading of HLA-A,B,C typing and screening. The propidium iodide (PI) method. Hum Immunol. 1982 Nov;5(3):225–231. doi: 10.1016/0198-8859(82)90135-5. [DOI] [PubMed] [Google Scholar]
  6. Carlquist J. F., Hammond E. H., Anderson J. L. Propagation and characterization of lymphocytes from rejecting human cardiac allografts. J Heart Transplant. 1988 Nov-Dec;7(6):397–406. [PubMed] [Google Scholar]
  7. Dunn M. J., Crisp S. J., Rose M. L., Taylor P. M., Yacoub M. H. Anti-endothelial antibodies and coronary artery disease after cardiac transplantation. Lancet. 1992 Jun 27;339(8809):1566–1570. doi: 10.1016/0140-6736(92)91832-s. [DOI] [PubMed] [Google Scholar]
  8. Duquesnoy R. J., Trager J. D., Zeevi A. Propagation and characterization of lymphocytes from transplant biopsies. Crit Rev Immunol. 1991;10(6):455–480. [PubMed] [Google Scholar]
  9. Frisman D. M., Fallon J. T., Hurwitz A. A., Dec W. G., Kurnick J. T. Cytotoxic activity of graft-infiltrating lymphocytes correlates with cellular rejection in cardiac transplant patients. Hum Immunol. 1991 Dec;32(4):241–245. doi: 10.1016/0198-8859(91)90086-o. [DOI] [PubMed] [Google Scholar]
  10. Grattan M. T., Moreno-Cabral C. E., Starnes V. A., Oyer P. E., Stinson E. B., Shumway N. E. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. JAMA. 1989 Jun 23;261(24):3561–3566. [PubMed] [Google Scholar]
  11. Hammond E. H., Ensley R. D., Yowell R. L., Craven C. M., Bristow M. R., Renlund D. G., O'Connell J. B. Vascular rejection of human cardiac allografts and the role of humoral immunity in chronic allograft rejection. Transplant Proc. 1991 Apr;23(2 Suppl 2):26–30. [PubMed] [Google Scholar]
  12. Hammond E. H., Yowell R. L., Nunoda S., Menlove R. L., Renlund D. G., Bristow M. R., Gay W. A., Jr, Jones K. W., O'Connell J. B. Vascular (humoral) rejection in heart transplantation: pathologic observations and clinical implications. J Heart Transplant. 1989 Nov-Dec;8(6):430–443. [PubMed] [Google Scholar]
  13. Hosenpud J. D., Shipley G. D., Wagner C. R. Cardiac allograft vasculopathy: current concepts, recent developments, and future directions. J Heart Lung Transplant. 1992 Jan-Feb;11(1 Pt 1):9–23. [PubMed] [Google Scholar]
  14. Jutte N. H., Heijse P., van Batenburg M. H., Vaessen L. M., Mochtar B., Balk A. H., Claas F. H., Weimar W. Donor heart endothelial cells as targets for graft infiltrating lymphocytes after clinical cardiac transplantation. Transpl Immunol. 1993;1(1):39–44. doi: 10.1016/0966-3274(93)90057-f. [DOI] [PubMed] [Google Scholar]
  15. Jutte N., Heyse P., van Batenburg M., Vaessen L., Mochtar B., Balk A., Claas F., Weimar W. Lysis of endothelial cells by graft-infiltrating lymphocytes after clinical heart transplantation. Transplant Proc. 1993 Feb;25(1 Pt 1):100–101. [PubMed] [Google Scholar]
  16. Kaufman C. L., Zeevi A., Kormos R. L., Zerbe T. R., Keenan R. J., Uretsky B. F., Griffith B. P., Hardesty R. L., Duquesnoy R. J. Propagation of infiltrating lymphocytes and graft coronary disease in cardiac transplant recipients. Hum Immunol. 1990 Jun;28(2):228–236. doi: 10.1016/0198-8859(90)90023-i. [DOI] [PubMed] [Google Scholar]
  17. Koskinen P. K., Krogerus L. A., Nieminen M. S., Mattila S. P., Häyry P. J., Lautenschlager I. T. Quantitation of cytomegalovirus infection-associated histologic findings in endomyocardial biopsies of heart allografts. J Heart Lung Transplant. 1993 May-Jun;12(3):343–354. [PubMed] [Google Scholar]
  18. Lavee J., Kormos R. L., Duquesnoy R. J., Zerbe T. R., Armitage J. M., Vanek M., Hardesty R. L., Griffith B. P. Influence of panel-reactive antibody and lymphocytotoxic crossmatch on survival after heart transplantation. J Heart Lung Transplant. 1991 Nov-Dec;10(6):921–930. [PubMed] [Google Scholar]
  19. Libby P., Salomon R. N., Payne D. D., Schoen F. J., Pober J. S. Functions of vascular wall cells related to development of transplantation-associated coronary arteriosclerosis. Transplant Proc. 1989 Aug;21(4):3677–3684. [PubMed] [Google Scholar]
  20. Narrod J., Kormos R., Armitage J., Hardesty R., Ladowski J., Griffith B. Acute rejection and coronary artery disease in long-term survivors of heart transplantation. J Heart Transplant. 1989 Sep-Oct;8(5):418–421. [PubMed] [Google Scholar]
  21. Ouwehand A. J., Vaessen L. M., Baan C. C., Jutte N. H., Balk A. H., Essed C. E., Bos E., Claas F. H., Weimar W. Alloreactive lymphoid infiltrates in human heart transplants. Loss of class II-directed cytotoxicity more than 3 months after transplantation. Hum Immunol. 1991 Jan;30(1):50–59. doi: 10.1016/0198-8859(91)90071-g. [DOI] [PubMed] [Google Scholar]
  22. Salomon R. N., Hughes C. C., Schoen F. J., Payne D. D., Pober J. S., Libby P. Human coronary transplantation-associated arteriosclerosis. Evidence for a chronic immune reaction to activated graft endothelial cells. Am J Pathol. 1991 Apr;138(4):791–798. [PMC free article] [PubMed] [Google Scholar]
  23. Suciu-Foca N., Reed E., Marboe C., Harris P., Yu P. X., Sun Y. K., Ho E., Rose E., Reemtsma K., King D. W. The role of anti-HLA antibodies in heart transplantation. Transplantation. 1991 Mar;51(3):716–724. doi: 10.1097/00007890-199103000-00033. [DOI] [PubMed] [Google Scholar]
  24. Thompson J. S., Overlin V., Severson C. D., Parsons T. J., Herbick J., Strauss R. G., Burns C. P., Claas F. H. Demonstration of granulocyte, monocyte, and endothelial cell antigens by double fluorochromatic microcytotoxicity testing. Transplant Proc. 1980 Sep;12(3 Suppl 1):26–31. [PubMed] [Google Scholar]
  25. Uretsky B. F., Murali S., Reddy P. S., Rabin B., Lee A., Griffith B. P., Hardesty R. L., Trento A., Bahnson H. T. Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone. Circulation. 1987 Oct;76(4):827–834. doi: 10.1161/01.cir.76.4.827. [DOI] [PubMed] [Google Scholar]
  26. Weber T., Kaufman C., Zeevi A., Zerbe T. R., Hardesty R. J., Kormos R. H., Griffith B. P., Duquesnoy R. J. Lymphocyte growth from cardiac allograft biopsy specimens with no or minimal cellular infiltrates: association with subsequent rejection episode. J Heart Transplant. 1989 May-Jun;8(3):233–240. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES