Tu20 - Chimerism and Bidirectional Alloresponses in Patients Receiving Lung Transplantation

Outcomes after lung transplantation (LuTx) are suboptimal mainly due to high rejection rates. Lung grafts carry T, B and antigen-presenting cells, which leading to graft-vs-host (GvH) and host-vs-graft (HvG) alloresponses. Dynamic repopulation and clonal distribution of T cells, the driver for alloresponses after LuTx, are largely under‐researched. We performed temporal analysis of immune cells in the serial bronchoalveolar lavage (BAL) of two patients. We utilized a combination of flow cytometry to distinguish donor- and recipient-derived cells by HLA specificity, with high-throughput TCR sequencing within pre-Tx lymphoid tissues to identify GvH- and HvG-reactive T cells defined by mixed lymphocyte reactions. Donor T/B/monocytes in BAL post-Tx were gradually replaced by the recipient. The turnover dynamic was faster in Pt4 compared to that in Pt1, especially for T cells. Donor CD8 T cells showed persistent high expression of TRM markers (CD69/CD103/CD49a) and low expression of effector T cell (Teff) marker CD28. However, recipient graft-infiltrating CD8 T cells gradually downregulating CD28 during the process of acquiring TRM features. An enrichment of HvG- compared to GvH-reactive sequences were observed in post-Tx BAL of Pt4, which was opposite as shown in Pt1. However, histology on the lung transbronchial biopsies described absence of rejection for both patients. Dynamic replacement of donor T cells by the recipient, and the presence and dominance of GvH- and HvG-reactive T cell sequences in lung allograft are likely providing valuable information to avoid miss diagnosis of early rejection by histology and revealing the underlying mechanisms of graft rejection and acceptance after LuTx.