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Enhancement of cytomegalovirus infection and acute rejection after allogeneic lung transplantation in the rat: virus-induced expression of major histocompatibility complex class II antigens.
J Heart Lung Transplant. 1996 Nov; 15(11):1108-19.JH

Abstract

BACKGROUND

Cytomegalovirus infection is considered a major complication after lung and heart-lung transplantation because it can trigger acute and chronic rejection. The potential mechanisms of lung transplant rejection induced by viral infection include the upregulation of expression of major histocompatibility complex antigens. To address this question, a model of rat cytomegalovirus infection and acute lung transplant rejection was established.

METHODS

Lewis inbred strain rats received syngeneic (n = 25) or allogeneic (Brown-Norway inbred rat strain, n = 38) orthotopic left-side lung transplants. Triple-drug immunosuppression with cyclosporin A, methylprednisolone, and azathioprine was given from postoperative days 1 through 10. Rat cytomegalovirus was inoculated intraperitoneally on postoperative day 3. Two control groups, those infected with cytomegalovirus (n = 15) and those without rat cytomegalovirus infection (n = 6) were treated with identical immunosuppressive regimens. Animals were sacrificed on postoperative days 11, 15, 18, 20, and 25. The salivary glands and both lungs were removed for pathologic and immunohistochemical investigations.

RESULTS

All animals inoculated with rat cytomegalovirus developed systemic viral infection on or after postoperative day 11, as confirmed by an assay of plaque-forming units and immunohistologic examination. Cytomegalovirus-induced expression of major histocompatibility complex class II antigens on vascular endothelial cells was seen in the nontransplanted lungs of rats, but no major histocompatibility complex class II antigens were detected on noninfected, nontransplanted lungs. Cytomegalovirus infection also was found to enhance major histocompatibility complex class II antigen expression on pneumocytes and leukocytes in rats. Acute rejection occurred in allogeneic transplants from postoperative days 15 through 25. The expression of class II antigens on endothelial cells, pneumocytes, and leukocytes was further enhanced during the course of allograft rejection in the cytomegalovirus-infected rats compared with the noninfected controls. In cytomegalovirus-positive rats, the rejection grade was higher than that in cytomegalovirus-negative rats on postoperative days 15 through 18.

CONCLUSIONS

Our results indicate that cytomegalovirus induces and enhances the expression of major histocompatibility complex class II antigens on endothelial cells, pneumocytes and leukocytes. Upregulation by cytomegalovirus infection may trigger or promote acute rejection by alloantigenic T-lymphocyte stimulation after lung transplantation. By this mechanism it may strongly influence the long-term course of lung transplant rejection.

Authors+Show Affiliations

Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8956120

Citation

You, X M., et al. "Enhancement of Cytomegalovirus Infection and Acute Rejection After Allogeneic Lung Transplantation in the Rat: Virus-induced Expression of Major Histocompatibility Complex Class II Antigens." The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, vol. 15, no. 11, 1996, pp. 1108-19.
You XM, Steinmüller C, Wagner TO, et al. Enhancement of cytomegalovirus infection and acute rejection after allogeneic lung transplantation in the rat: virus-induced expression of major histocompatibility complex class II antigens. J Heart Lung Transplant. 1996;15(11):1108-19.
You, X. M., Steinmüller, C., Wagner, T. O., Bruggeman, C. A., Haverich, A., & Steinhoff, G. (1996). Enhancement of cytomegalovirus infection and acute rejection after allogeneic lung transplantation in the rat: virus-induced expression of major histocompatibility complex class II antigens. The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, 15(11), 1108-19.
You XM, et al. Enhancement of Cytomegalovirus Infection and Acute Rejection After Allogeneic Lung Transplantation in the Rat: Virus-induced Expression of Major Histocompatibility Complex Class II Antigens. J Heart Lung Transplant. 1996;15(11):1108-19. PubMed PMID: 8956120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhancement of cytomegalovirus infection and acute rejection after allogeneic lung transplantation in the rat: virus-induced expression of major histocompatibility complex class II antigens. AU - You,X M, AU - Steinmüller,C, AU - Wagner,T O, AU - Bruggeman,C A, AU - Haverich,A, AU - Steinhoff,G, PY - 1996/11/1/pubmed PY - 1996/11/1/medline PY - 1996/11/1/entrez SP - 1108 EP - 19 JF - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JO - J. Heart Lung Transplant. VL - 15 IS - 11 N2 - BACKGROUND: Cytomegalovirus infection is considered a major complication after lung and heart-lung transplantation because it can trigger acute and chronic rejection. The potential mechanisms of lung transplant rejection induced by viral infection include the upregulation of expression of major histocompatibility complex antigens. To address this question, a model of rat cytomegalovirus infection and acute lung transplant rejection was established. METHODS: Lewis inbred strain rats received syngeneic (n = 25) or allogeneic (Brown-Norway inbred rat strain, n = 38) orthotopic left-side lung transplants. Triple-drug immunosuppression with cyclosporin A, methylprednisolone, and azathioprine was given from postoperative days 1 through 10. Rat cytomegalovirus was inoculated intraperitoneally on postoperative day 3. Two control groups, those infected with cytomegalovirus (n = 15) and those without rat cytomegalovirus infection (n = 6) were treated with identical immunosuppressive regimens. Animals were sacrificed on postoperative days 11, 15, 18, 20, and 25. The salivary glands and both lungs were removed for pathologic and immunohistochemical investigations. RESULTS: All animals inoculated with rat cytomegalovirus developed systemic viral infection on or after postoperative day 11, as confirmed by an assay of plaque-forming units and immunohistologic examination. Cytomegalovirus-induced expression of major histocompatibility complex class II antigens on vascular endothelial cells was seen in the nontransplanted lungs of rats, but no major histocompatibility complex class II antigens were detected on noninfected, nontransplanted lungs. Cytomegalovirus infection also was found to enhance major histocompatibility complex class II antigen expression on pneumocytes and leukocytes in rats. Acute rejection occurred in allogeneic transplants from postoperative days 15 through 25. The expression of class II antigens on endothelial cells, pneumocytes, and leukocytes was further enhanced during the course of allograft rejection in the cytomegalovirus-infected rats compared with the noninfected controls. In cytomegalovirus-positive rats, the rejection grade was higher than that in cytomegalovirus-negative rats on postoperative days 15 through 18. CONCLUSIONS: Our results indicate that cytomegalovirus induces and enhances the expression of major histocompatibility complex class II antigens on endothelial cells, pneumocytes and leukocytes. Upregulation by cytomegalovirus infection may trigger or promote acute rejection by alloantigenic T-lymphocyte stimulation after lung transplantation. By this mechanism it may strongly influence the long-term course of lung transplant rejection. SN - 1053-2498 UR - https://www.unboundmedicine.com/medline/citation/8956120/Enhancement_of_cytomegalovirus_infection_and_acute_rejection_after_allogeneic_lung_transplantation_in_the_rat:_virus_induced_expression_of_major_histocompatibility_complex_class_II_antigens_ L2 - https://medlineplus.gov/cytomegalovirusinfections.html DB - PRIME DP - Unbound Medicine ER -