Decreased donor-specific cytotoxic T cell precursor frequencies one year after clinical lung transplantation do not reflect transplantation tolerance: A comparison of lung transplant recipients with or without bronchiolitis obliterans syndrome

Background. Decreased in vitro T cell alloreactivity, demonstrated by decre ased frequencies of peripheral blood donor-specific T cell precursors, may reflect a tolerant state after transplantation and lower the risk for devel opment of chronic graft dysfunction. It is unknown whether a decrease in do nor-specific T cell frequencies also occurs after clinical lung transplanta tion and if such a decrease lowers the risk for bronchiolitis obliterans sy ndrome (BOS), a hallmark of chronic graft dysfunction. Therefore, we compar ed changes in posttransplant donor-specific cytotoxic T lymphocyte (CTLp) a nd helper T lymphocyte precursor (HTLp) frequencies in lung allograft recip ients with good graft function and in recipients with BOS. Methods. Donor and third party specific CTLp and HTLp frequencies were dete rmined by limiting dilution assay in pre- and posttransplant (1 year) perip heral blood samples of lung allograft recipients with good graft function ( n=13) and BOS (n=10). Results. In recipients with good graft function, mean donor-specific CTLp f requencies decreased after transplantation (183 vs. 16 precursors before an d after transplantation, respectively). Additionally, HTLp frequencies decr eased but this was not specific for donor alloantigens because third party- specific HTLp frequencies decreased also. Surprisingly, recipients with BOS also showed a decrease in mean donor-specific CTLp frequencies after trans plantation (332 vs. 49 precursors before and after transplantation, respect ively). Again, HTLp frequencies decreased nonspecifically. Conclusions. We conclude that donor-specific CTLp frequencies decrease afte r lung transplantation, but that this does not result in transplantation to lerance protecting the lung against the development of chronic graft dysfun ction.