Improving the Early Immune Parameters of Lung Transplantation in the Pig Model by Treating Both Donors and Recipients with Corticosteroids
Résumé
Purpose: The innate allogeneic immune response in lung transplantation contributes to both the development of primary graft dysfunction and the activation of the adaptive immune response, which can lead to rejection. Therefore, effectively targeting this innate immune response is crucial for better outcomes. The current perioperative immunomodulatory treatment includes a corticosteroid injection administered to the recipient during surgery. However, the immunological benefit of extending this treatment to the donor, a practice that is not widely adopted, remains unknown. Methods: To analyze the immune parameters affected by donor preconditioning, we used a porcine cross-circulation platform, consisting of an ex vivo donor lung (D) connected to the circulation of a recipient pig (R) whose leukocytes were fluorescently labeled. We compared 3 groups of pig pairs: i) untreated D and R, ii) treated R only, iii) treated D and R. Tissue samples from the ex vivo graft were collected during the first ten hours of reperfusion. The immune cell composition was analyzed by flow cytometry and immunohistochemistry. Gene expression was evaluated by RT-PCR. Results: Recipient treatment, whether or not combined with donor treatment, similarly reduced the activation profile of recruited CD14pos and CD16pos monocyte subsets. Interestingly, we found that donor’s preconditioning reduced the representation of both donor- and recipient-derived CD3pos T cells in the graft and improved the anti-inflammatory profile of alveolar macrophages, at least during the first 10 hours of donor/recipient interaction. Donor preconditioning was associated with decreased expression of genes encoding T cell-attracting chemokines (CXCL9, CXCL10, and CXCL11) by alveolar macrophages. Conclusion: These results indicate that preconditioning the donor lung with corticosteroids improves the early immunological status of lung grafts during LT and could have a positive impact on clinical outcomes.