118.7: The role of tertiary lymphoid structures in aged swine on the progression of pulmonary ischemia-reperfusion injury

Background: Tertiary lymphoid structures (TLS), which are induced in tissues by bacterial and viral infections and various autoimmune diseases, have attracted attention for their involvement in post-transplant pathogenesis. This may be due in part to the fact that TLS are more likely to be induced in aged organs and may be a factor promoting organ failure or rejection. Although xenotransplantation is usually performed with organs from young animals, it is important to evaluate the pattern of TLS induction over time in transplanted porcine organs for long-term outcome after xenotransplantation. In this study, as a first step to evaluate the pattern of TLS induction in porcine organs, we used young and aged pigs to evaluate the relationship between inducible bronchus-associated lymphoid tissue (iBALT), an intrapulmonary TLS induced during pulmonary ischemia-reperfusion injury, and lung injury at different ages. Methods: Warm ischemia was induced by clamping the left pulmonary artery and vein for 90 minutes. Pulmonary functions were assessed by blood gas analysis, chest x-ray films (CXRs), and lung biopsies. Pigs older than 3 years were used as the old group (n=4), while pigs around 6 months of age were used as the young group (n=5). Serum cytokine levels (TNF-α, IL-6, HMGB1) and oxidative stress were measured to characterize the inflammatory response to pulmonary IRI. Results: Although direct assessment of lung injury using left PV blood showed a slightly better P/F ratio in the aging group (323 ± 68 vs. 292 ± 33 mmHg at 2 days), there were no significant differences in preoperative data between the two groups, including the degree of lung injury based on arterial and left PV blood gas, CXRs. Histologic scores calculated by cellular infiltration, intra-alveolar edema, fibrin exudation, and hemorrhage showed no significant differences between the two groups. Limited iBALT induction was observed only in the aging groups. In addition, serum levels of proinflammatory antioxidant cytokines and showed slightly higher levels in the aging group, although there were no significant differences between two groups. Conclusions: In this model, age difference alone did not affect the progression of lung injury, including iBALT induction. These results indicate that activation of the innate immune system alone is not sufficient for the progression of pulmonary IRI and induction of iBALT. Future studies will be performed in lung transplantation models, taking into account the involvement of cold ischemia, acquired immune system or lymphangiogenesis/angiogenesis.