Lung transplants are particularly vulnerable to rejection, due to continual exposure to the external environment. Particulates can trigger inflammation, and pathogens, including viruses, bacteria, and fungi, may promote heterologous immunity. Brain death in the organ donor can cause lung inflammation, which can negatively impact new transplant function. Other factors that contribute to lung allograft rejection are ischemia/reperfusion injury and HLA immunogenicity of the graft. Furthermore, lack of a bronchial artery circulation after surgery may compromise allograft function. While these factors are proinflammatory, lungs also possess unique antiinflammatory properties, including antigen-presenting CD11c⁺ cells that have the capacity to suppress T cell activation through the increased production of indoleamine 2,3-dioxygenase (IDO). Additionally, Krupnick et al. (10) have described a CD44⁺CD62L⁺CCR7⁺ CD8⁺ Treg that infiltrates lung transplants and is required for costimulation-induced lung allograft acceptance. The proposed mechanism of CD8⁺ Treg action is mediated through IFN-γ limitation of alloreactive CD4⁺ T cell proliferation and the local upregulation of NO. The chemokine receptor CCR7 on CD8⁺ Tregs may bind to CCL21 on CD11c⁺ dendritic cells to dampen immune responses.