ABSTRACT

Transplantation of the lungs represents an interesting immunological paradox as the mucosal interface maintains a relatively immunoprivileged environment to avoid hyperactivity to inhaled antigens or allergens. Despite this, lung allografts seem particularly immunogenic in that even with the most aggressive immunosuppression a high proportion undergo rejection when compared to renal or cardiac allografts. In this review, we summarize the current progress in the development of strategies aimed at inducing immunological tolerance and our understanding of the role and complexity of the regulatory T (Treg) cells that maintain such tolerance. We also consider the role that dendritic cells play in eliciting either graft rejection or tolerance, and how they may be manipulated to provide tolerogenic signals. Finally, we look at how the grafted tissue may upregulate protective genes under the influence of Treg cells, and examine the extent to which conventional immunosuppressive agents interfere with any one of these components of tolerance as a plausible mechanism to explain chronic rejection.