Frontiers in immunology · 2026
Longitudinal profiling of γδ T cell dynamics after human lung transplantation links donor and recipient subsets to clinical outcomes.
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Wang Joshua H, Young Tyla, Long Katherine D, Jiao Wenyu, Bay Muntnich Constanza, Prada Rey Adriana, Khwajazadah Morcel, Mohan Vineetha, Rogers Kortney, Valena Arnold, Costa Joseph, Benvenuto Luke, Sonett Joshua, Lemaitre Philippe, D'Ovidio Frank, Arcasoy Selim, Fu Jianing
Аннотация
INTRODUCTION: Long-term survival after lung transplantation lags behind that of other solid organ transplants, underscoring the need to better understand its complex immune responses to prevent complications and improve clinical outcomes. While most post-transplant immune studies on T lymphocytes have focused on αβ T cells, the role of mucosal-tissue-enriched γδ T cells remains largely unexplored in lung transplantation.
METHODS: We performed a longitudinal analysis of the presence, chimerism, and phenotype of γδ T cells in 13 lung transplant recipients, tracking their dynamics in peripheral blood and bronchoalveolar lavage (BAL) for up to 3 years after transplantation.
RESULTS: Patients undergoing bilateral transplantation exhibited a significantly higher percentage of γδ T cells among total T cells in BAL compared to single-lung recipients. In circulation, higher peak levels of donor-derived γδ T cells were associated with a trend toward higher circulating donor γδ T cell counts and lower incidence of acute cellular rejection, suggesting a protective systemic role. While within BAL, a more rapid turnover of recipient γδ T cells was associated with significantly delayed onset of infection and improved pulmonary function. Over time, recipient γδ T cells in BAL showed a phenotypic shift from effector (CD28high) toward tissue-resident memory (TRM; CD69+/CD103+/CD49a+) phenotypes. As expected, TRM phenotypes were more prevalent in BAL than in blood for both donor and recipient γδ T cells. Interestingly, rapidly infiltrating recipient γδ T cells in BAL were less TRM-like. Furthermore, infection was associated with an enrichment of recipient-derived effector memory γδ T cells in circulation, suggesting their involvement in blood-graft crosstalk.
DISCUSSION: Overall, our longitudinal study demonstrates the distinct local and systemic dynamics of donor and recipient γδ T cells after human lung transplantation and identifies several phenotypes and kinetics linked to clinical outcomes.
METHODS: We performed a longitudinal analysis of the presence, chimerism, and phenotype of γδ T cells in 13 lung transplant recipients, tracking their dynamics in peripheral blood and bronchoalveolar lavage (BAL) for up to 3 years after transplantation.
RESULTS: Patients undergoing bilateral transplantation exhibited a significantly higher percentage of γδ T cells among total T cells in BAL compared to single-lung recipients. In circulation, higher peak levels of donor-derived γδ T cells were associated with a trend toward higher circulating donor γδ T cell counts and lower incidence of acute cellular rejection, suggesting a protective systemic role. While within BAL, a more rapid turnover of recipient γδ T cells was associated with significantly delayed onset of infection and improved pulmonary function. Over time, recipient γδ T cells in BAL showed a phenotypic shift from effector (CD28high) toward tissue-resident memory (TRM; CD69+/CD103+/CD49a+) phenotypes. As expected, TRM phenotypes were more prevalent in BAL than in blood for both donor and recipient γδ T cells. Interestingly, rapidly infiltrating recipient γδ T cells in BAL were less TRM-like. Furthermore, infection was associated with an enrichment of recipient-derived effector memory γδ T cells in circulation, suggesting their involvement in blood-graft crosstalk.
DISCUSSION: Overall, our longitudinal study demonstrates the distinct local and systemic dynamics of donor and recipient γδ T cells after human lung transplantation and identifies several phenotypes and kinetics linked to clinical outcomes.