ABSTRACT
I. Introduction Lung transplantation remains the hope for many incurable pulmonary diseases, such as cystic fibrosis, pulmonary fibrosis, and chronic obstructive pulmonary disease. Remarkable progress has been made in improving outcomes, although the incidence of acute rejection remains over 50% in the first year, and the five year graft survival is still less than 50% due primarily to the development of chronic rejection and graft dysfunction (1). Many of the significant advances made in solid organ transplantation, including lung, have been the result of advances in immunology. In 1905 Alexis Carrel proclaimed that the surgical challenges of organ transplantation had been solved, but it was not until the implementation of immunosuppression that solid organ transplantation became a viable treatment option for patients with end-stage disease (2,3). In the United States, there are nearly 30,000 solid organ transplants performed yearly. Lung transplant recipients face the worst post-transplant survival statistics of the solid organs except small bowel and provide the biggest challenge for immunology to continue to improve outcomes (1). Acute rejection mediated by alloreactive T and B cells is usually treatable with immunosuppression but has been found to be an important risk factor for chronic rejection. Chronic rejection is characterized by the development of obliterative bronchiolitis (OB) in allografts and manifests as bronchiolitis obliterans syndrome (BOS) in humans with no effective treatment. Previous studies support a role for alloreactive T and B cells in the development of BOS, but recent studies highlight a role for autoimmunity in the pathogenesis of the rejection response (4-6). However, many of the specific mechanisms are unknown (reviewed in Refs. 1,7).
