Immunogenomic landscape of the T cell repertoire after human lung transplantation and its clinical relevance

Long-term lung transplant survival is limited by rejection and infection, processes driven by T cells whose post-transplant dynamics are poorly defined. Using flow cytometry and T cell receptor (TCR) sequencing of serial bronchoalveolar lavage (BAL) and peripheral blood samples, we monitored T cell chimerism, phenotypes, and clonotypic dynamics in a small cohort of lung transplant recipients. We identified alloreactive clones via mixed lymphocyte reaction/TCR-seq pairing and microbial-reactive clones via database matching. We found a recipient-derived tissue-resident memory T cell (TRM) repertoire progressively established in BAL, stabilized by pre-existing, multi-tissue-shared clones. Clonal graft–blood overlap was significantly mediated by CD8 + non-alloreactive recipient T cells of multi-tissue origin. During infection, pathogen-specific clones expanded in BAL, enriched within the non-alloreactive repertoire. A higher host-versus-graft to graft-versus-host T-cell ratio was associated with accelerated recipient repopulation, and enrichment of host-versus-graft clones in BAL was associated with early rejection and pulmonary dysfunction. Our exploratory findings provide novel insight into TRM establishment and specialization after lung transplantation and highlight TCR features that warrant further validation as potential correlates of graft outcomes.