Abstract
Since the 1980 s, lung transplantation has evolved into an established therapeutic procedure, due to advancements in surgical techniques and the introduction of immunosuppressants such as cyclosporine. Despite improved short-term outcomes, the long-term prognosis remains limited, primarily due to immunological complications. With a median survival of approximately six years, the lung is the most immunogenic solid organ, owing to its constant exposure to environmental antigens and its extensive vascular endothelial surface. After lung transplantation, various forms of alloreactivity, including T cell-mediated acute and chronic rejection, play a central role. Additionally, humoral immune responses, characterised by the production of donor-specific and non-HLA antibodies, contribute significantly to graft injury. Recurrent tissue damage, such as ischemia reperfusion injury, leads to the exposure of cryptic antigens, promotes autoreactive processes, and facilitates the formation of tertiary lymphoid organs. These mechanisms sustain persistent inflammation, ultimately resulting in chronic graft dysfunction. Rejection reactions remain a major challenge. Acute forms, such as cellular and humoral rejection, require rapid and targeted therapies to prevent irreversible damage. Chronic rejection, particularly chronic lung allograft dysfunction (CLAD), progressively impairs lung function. In the main phenotypes of CLAD, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS), are crucial for prognosis and treatment. Nevertheless, therapeutic options remain limited, and retransplantation is often the last resort. Immunosuppressive therapy forms the cornerstone of rejection prevention, and typically employs a triple combination of calcineurin inhibitors, antiproliferative agents, and corticosteroids. Induction therapy frequently involves monoclonal or polyclonal antibodies. Modern strategies aim to effectively suppress immune responses while minimising severe side effects, such as infections, malignancies, and nephrotoxicity. Future research will focus on personalised immunosuppressive strategies, optimised diagnostics, and innovative therapies to improve the long-term prognosis of lung transplant recipients.