Innate immunity in heart transplantation.

PURPOSE OF REVIEW: Cardiac transplantation is the treatment of choice for end-stage heart failure, but its efficacy is limited by the development of cardiac allograft vasculopathy (CAV). Although the adaptive immune system is efficiently suppressed by conventional drugs, the innate immune system is largely unaffected. The innate response may contribute both to stimulation of the adaptive response and to the future development of CAV.

RECENT FINDINGS: Stimulation of Toll-like receptors by endogenous ligands released in response to ischemia/reperfusion causes an inflammatory milieu favorable to graft rejection and unfavorable to tolerance. New evidence suggests that natural killer cells have previously unknown memory-like features and are capable of graft rejection. Their role in rejecting the cardiac allograft has previously been underestimated. Complement deposition may also contribute to acute cellular rejection and CAV.

SUMMARY: The innate immune system is an important but neglected component of allograft rejection. Drugs that target Toll-like receptors, natural killer cells and complement may play an important role in preventing CAV and achieving tolerance to cardiac allografts.