ABSTRACT
Despite the many advances in the field of lung transplantation, the average time of survival after a transplant is only 5.5 years and has not improved significantly over the past 2 decades. 1 Chronic rejection in the form of bronchiolitis obliterans syndrome (BOS) remains the primary limitation to long-term survival in lung transplant recipients. 1 Medical management after lung and other solid-organ transplants has thus far been characterized by nonspecific suppression of T-cell responses to antigens. Calcineurin inhibitor therapy revolutionized the world of organ transplantation in the 1970s and clearly impairs T-cell responses to alloantigen to some degree, thereby resulting in decreased acute cellular rejection (ACR). However, it also results in impaired T-cell responses to infectious pathogens and fails to prevent chronic rejection. Induction of tolerance remains the “holy grail” of transplant immunology because it would result in immune recognition of alloantigen coupled with the lack of an inflammatory response to that antigen specifically. That tolerance is an active immune process requiring not only the absence of certain cellular events but also the presence of others is becoming increasingly clear. In addition to induction of tolerance, the ability to direct immunosuppressive therapy in a manner targeted toward suppression of specific alloantigen responses would be ideal therapeutically. In many ways, the field of lung transplantation stands to benefit most from these potential advances in transplant pharmacotherapy because chronic rejection has a greater impact on the survival of lung allografts than on that of other transplanted solid organs, such as the heart, liver, or kidney. For this reason, novel immunologic therapies for use in transplantation may be best tested in lung transplant recipients, and it is critical that transplant pulmonologists explore such therapies in an effort to improve long-term outcomes in such patients.
