Upregulation of T-helper 1 cytokines and chemokine expression in post-transplant airway obliteration

The major obstacle to long-term survival after lung transplantation is chro nic graft dysfunction manifest as bronchiolitis obliterans. Since the early stages are characterized by proliferation of itinerant cells (lymphocytes and macrophages), we hypothesized that cytokines and chemokines may play a role in the development of the fibroproliferative process. In a heterotopic rat tracheal transplant model, we studied isografts and allografts 3, 7, a nd 21 d after transplantation as representative time points for the triphas ic time course in the evolution of allograft airway obliteration. Using a s emiquantitative RT-PCR technique, intragraft gene expression of T-helper 1 (Th1)- and Th2-type cytokines and of C-C and C-X-C chemokines was examined. The results of our study show a distinct pattern of cytokine and chemokine gene expression in the development of post-transplant airway obliteration. Allografts, in contrast to isografts, showed a strong and persistent Th1-t ype response (expression of interleukin-2 and interferon-gamma genes), even after fibrous airway obliteration was complete, suggesting an ongoing allo -immune process until late in the fibroproliferative stage. RANTES and MCP- 1 were also upregulated late after transplantation, whereas MIP-2 upregulat ion occurred early post-transplant and was not restricted to allografts alo ne, which might reflect alloantigen-independent processes after transplanta tion that are present in both allografts and isografts.