Human allogeneic CD2+lymphocytes activate airway-derived epithelial cells to produce interleukin-6 and interleukin-8. Possible role for the epithelium in chronic allograft rejection

Autor: P Borger, Gh Koeter, Henk F. Kauffman, J. A. B. Timmerman, J Scholma
Jazyk: angličtina
Rok vydání: 2002
Předmět:
Zdroj: Journal of Heart and Lung Transplantation, 21(5):PII S1053-2498(01)00418-1, 567-575. ELSEVIER SCIENCE INC
ISSN: 1053-2498
Popis: Background: The adhesion of lymphocytes to the epithelium and the release of proinflammatory cytokines are important features observed during acute and chronic allograft rejection. Development of chronic rejection in lung-transplantation patients is preceded by high levels of interleukin (IL)-6 and IL-8 protein in the bronchoalveolar lavage. Therefore, we studied the expression of IL-6 and IL-8 in cocultures of epithelial cells and allogeneic lymphocytes. Methods: IL-6 and IL-8 protein levels were determined in supernatants of the airway-derived epithelial cell line A549 and in primary epithelial cells obtained from lung-brushings after coculturing with autologous and allogeneic lymphocytes. Transcriptional mechanisms were detected by transient transfections. Results: Coculture-supernatants of epithelial cells and allogeneic CD2+ lymphocytes show high levels of IL-6 and IL-8 protein due to transcriptional activation of the respective genes in epithelial cells. Highest productions were measured when the epithelial-cell:lymphocyte ratio was 1:10. Highly purified CD4+ and/or CD8+ cells were unable to induce the same response as observed with the total lymphocyte-population. Depletion of CD4+ and/or CD8+ had no effect on the IL-6 and IL-8 production induced by the total CD2+ lymphocyte-population. However, depletion of CD56+ cells diminished the lymphocyte-induced IL-6 and IL-8 production by > 75%. Conclusion: These data show that allogeneic CD2+ lymphocytes are able to activate lung-derived epithelial cells, resulting in the release of proinflammatory cytokines, which have a prominent role in chronic allograft rejection observed in lung-transplantation patients.
Databáze: OpenAIRE