Inadequate antibody response against respiratory viral infection in long-surviving rat lung allografts

Abstract

Lung transplant recipients suffer from a high number of viral infections. It has been suggested that the defense against viral infections is impaired in lung transplants. Therefore, we investigated in rat lung transplants whether antibody responses against an intrapulmonary viral infection were impaired in 3 groups of rats with: (1) BN-to-LEW allogeneic lung transplants, (2) LEW-to-LEW syngeneic lung transplants, and (3) nontransplanted LEW lungs. All rats (including those with nontransplanted, normal lungs) were treated with cyclosporine on days 2 and 3 after operation; this treatment is adequate to induce permanent graft acceptance of the allografts. Six months after transplantation, viral infections with Sendai virus (parainfluenza type I) were induced intratracheally. At day 0, immediately before infection, and at days 4, 7, 21, and 56 after infection, 4 rats in each group were killed for histological evaluation of the lungs. The number of antibody-positive cells in the bronchus-associated lymphoid tissue (BALT) in the lungs and in the spleen, and presence of the virus in the lungs were determined by immunohistology. Serum antibody titers were followed for 56 days after infection. The allogeneically transplanted lungs failed to respond adequately against the virus: the number of antibody-positive cells in the BALT did not increase after infection, serum antibody titers were hardly detectable, and virus was present in the airways of the lungs up to day 21 after infection. In contrast, in the syngeneically and nontransplanted lungs, the number of antibody-forming cells in the BALT increased steeply until day 7, serum antibody titers rose until day 14, and virus could be detected only on day 4 after infection. This study shows that in rat lung allografts, both the local antibody production in the BALT and the systemic antibody response against a respiratory viral infection are inadequate. As a consequence, the virus is present longer in these allografted lungs and can exert its damaging effect over a longer period of time. These results may explain why lung transplants are so susceptible to viral infections.