Long-term antibody production in canine lung allografts: implications in pulmonary immunity and asthma.

Abstract

Lung transplant recipients can become asthmatic if they receive donor lungs from asthmatics. The maintenance of sensitivity in the lung allograft for inhaled allergens supports the concept that the mechanisms responsible for asthma are localized in the lungs, with a minimal systemic component. Pulmonary immunity to inhaled allergens is one mechanism which could be localized to the lung that would play a pivotal role in asthma. For example, the continued production of antibody to inhaled allergens in a human lung allograft could cause asthmatic responsiveness in the recipient. In this study, we tested the hypothesis that pulmonary immune cells continue to produce antibody in a canine allograft lung for relatively long times after transplantation. This was accomplished by immunizing four dogs by instillation of keyhole limpet hemocyanin (KLH) into a single lung lobe. After two challenges, the immunized lung from each dog was transplanted into a nonimmune recipient. Immune evaluations of recipients showed that anti-KLH antibody continued to be produced only in the donor lung for as long as 320 days after transplantation. Data from this study suggest that (1) immune cells in the lung can function independently from systemic immunity, (2) antibody production in the lung makes a significant contribution to blood antibody levels, and (3) immune cells in donor lungs can continue to produce antibody for relatively long times after transplantation. Therefore, immune cells in donor lungs from asthmatics could continue to produce antibody to allergens after transplantation, and this locally produced antibody may be responsible for the asthmatic responses observed in the recipients.