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 governed by T cells, the posttransplant dynamics of which 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 sequence pairing and microbial-reactive clones via database matching. We found a recipient-derived tissue-resident memory T cell repertoire progressively established in BAL, stabilized by preexisting, multitissue-shared clones. Clonal graft-blood overlap was significantly mediated by CD8+ nonalloreactive recipient T cells of multitissue origin. During infection, pathogen-specific clones expanded in BAL, enriched within the nonalloreactive repertoire. A higher host-vs-graft to graft-vs-host T cell ratio was associated with accelerated recipient repopulation, and enrichment of host-vs-graft clones in BAL was associated with early rejection and pulmonary dysfunction. Our exploratory findings provide novel insight into tissue-resident memory T cell establishment and specialization after lung transplantation and highlight TCR features that warrant further validation as potential correlates of graft outcomes.