These data suggest that T cells from LTx recipients are sensitized to mismatched HLA class I antigens. The sensitization was significantly higher in LTx recipients with BOS compared with LTx recipients without BOS. Strategies to block T-cell responses generated by indirect allorecognition after lung transplantation may provide a means for the prevention or treatment of BOS in LTx recipients.

A correlation between indirect allorecognition of mismatched donor HLA class I peptides and development of bronchiolitis obliterans syndrome (BOS) after lung transplantation has been previously observed. The aim of this study was to determine whether there was a correlation between indirect allorecognition of mismatched donor HLA class II peptides and development of BOS after lung transplantation. Peripheral blood mononuclear cells from nine BOSπ and nine BOSlung transplant recipients were cultured with synthetic peptides corresponding to the b-chain hypervariable region of a mismatched donor HLA-DR molecule. Then, proliferative alloreactivity as well as frequency of alloreactive T cells were determined. In addition, the immunodominant epitopes from the donor HLA-DR molecules were identified in selected patients. T cells from BOSπ patients showed a dose-dependent proliferative alloreactivity against donor HLA-DR peptides that was significantly higher than that observed in BOS-patients (pΩ0.001). Similarly, the frequency of HLA-DR alloreactive T cells was significantly higher in BOSπ patients than in BOS-patients (pΩ0.001). This T-cell alloreactivity was directed against a single immunodominant HLA-DR peptide. These results suggest that indirect alloreactivity to donor HLA class II molecules may play a role in the pathogenesis of BOS after lung transplantation.

No abstract

The results suggest that LTx and RTx recipients undergo rejection despite DSM. The development of DSM may not be a prerequisite for normal allograft function. Once DSM is established, the presence of the allograft is not required for maintenance of chimerism. DST facilitated the development of DSM in RTx recipients. Direct correlation was not observed between the development of DSM and allograft function in either DST or nontransfused RTx recipients.

These results show that sensitization of CD4+ T cells against the mismatched HLA-A2 alloantigen precedes the development of anti-HLA antibodies as well as OAD, suggesting an important role for alloreactive CD4(+) T-cell activation and alloantibody development in the immunopathogenesis of OAD.