Fig. 1. Diagram depicting mechanisms mediating primary graft dysfunction, rejection and the induction of tolerance.

In the context of ischemia-reperfusion injury (IRI), damage-associated molecular patterns (DAMPs) release contributes to the infiltration of neutrophils into the graft. Recipient-derived CCR2⁺ monocytes and donor alveolar macrophages facilitate neutrophil recruitment from blood vessels to the injured lung graft. Once activated, neutrophils in concert with mast cells can produce pro-inflammatory mediators such prostaglandins (PGs), interleukin (IL)-1β and IL-6, which can promote primary graft dysfunction. Allorecognition occurs locally within lung allografts through the engagement of antigen presenting cells (APCs) and T lymphocytes. Activated neutrophils can also express co-stimulatory molecules, which further promote the activation of naïve CD4⁺ T cells. Lymphocytes regulate outcomes after LTx. CD4⁺Th1, CD4⁺Th17, γδ IL17⁺, CD8⁺Th17 and CD8⁺ cytotoxic T cells promote graft loss, while regulatory CD4⁺Foxp3⁺ T cells (Tregs), CD8⁺CD44⁺CD62L⁺ central memory T cells and also NK cells can prevent rejection.