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 SYNDROME1

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Abstract
Decreased in vitro T cell alloreactivity, demonstrated by decreased frequencies of peripheral blood donor-specific T cell precursors, may reflect a tolerant state after transplantation and lower the risk for development of chronic graft dysfunction. It is unknown whether a decrease in donor-specific T cell frequencies also occurs after clinical lung transplantation and if such a decrease lowers the risk for bronchiolitis obliterans syndrome (BOS), a hallmark of chronic graft dysfunction. Therefore, we compared changes in posttransplant donor-specific cytotoxic T lymphocyte (CTLp) and helper T lymphocyte precursor (HTLp) frequencies in lung allograft recipients with good graft function and in recipients with BOS. Donor and third party specific CTLp and HTLp frequencies were determined by limiting dilution assay in pre- and posttransplant (1 year) peripheral blood samples of lung allograft recipients with good graft function (n=13) and BOS (n=10). In recipients with good graft function, mean donor-specific CTLp frequencies decreased after transplantation (183 vs. 16 precursors before and after transplantation, respectively). Additionally, HTLp frequencies decreased 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 transplantation (332 vs. 49 precursors before and after transplantation, respectively). Again, HTLp frequencies decreased nonspecifically. We conclude that donor-specific CTLp frequencies decrease after lung transplantation, but that this does not result in transplantation tolerance protecting the lung against the development of chronic graft dysfunction.