ArticleThe Journal of clinical investigation2019
Bronchus-associated lymphoid tissue-resident Foxp3+ T lymphocytes prevent antibody-mediated lung rejection.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06112951 (The Use of Extracorporeal Photopheresis as Immunomodulatory Therapy of Subclinical Antibody-mediated Rejection After Lung Transplantation), which is not on this map. Cited by 59 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Use of Extracorporeal Photopheresis as Immunomodulatory Therapy of Subclinical Antibody-mediated Rejection After Lung Transplantation: a Prospective RCT
Who cites it
59 citing papers in PubMed, 92 citations in OpenAlex.
- Multiplex immunofluorescence in the identification of immune cell compositions in rejection, bronchus-associated lymphoid tissue, and infection in lung allograft tissue.Virchows Archiv : an international journal of pathology · 2026Article
- B6 Donor Lungs Develop Chronic Lung Allograft Dysfunction-like Pathology Across Histocompatibility Mismatches in Murine Lung Transplantation.Transplantation direct · 2026Article
- The Myeloid-T Lymphocyte Axis in Chronic Lung Allograft Rejection: Emerging Insights into the Immune Circuitry Driving Fibrosis.Results and problems in cell differentiation · 2026Review
- B cells and iBALT in TB immunity & pathogenesis.Frontiers in immunology · 2026Review
- Multi-site cytokine levels are predictive of primary graft dysfunction following lung transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2026Article
- Tolerogenic lung allograft microenvironment suppresses pathogenic tissue remodeling following respiratory virus infection in mice.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- Emerging roles for complement in lung transplantation.The Journal of clinical investigation · 2025Review
- The roles of tertiary lymphoid structures in orchestrating immune responses in peripheral organs.Inflammation and regeneration · 2025Review
- Extracorporeal Photopheresis in Lung Transplantation: Present Applications and Emerging Research.Transplantation direct · 2025Article
- Defensive tolerance drives the reprogramming and dysfunction of infiltrating pathogenic B cells assuring the maintenance of tolerance.Research square · 2025Article
- The search for peripheral tolerance in lung transplantation.Current opinion in pulmonary medicine · 2025Review
- Maintenance of graft tissue-resident Foxp3+ cells is necessary for lung transplant tolerance in mice.The Journal of clinical investigation · 2025Article
- iPSCs engrafted in allogeneic hosts without immunosuppression induce donor-specific tolerance to secondary allografts.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Chronic Lung Allograft Dysfunction: Clinical Manifestations and Immunologic Mechanisms.Transplantation · 2025Review
- Article
- Bronchus-associated lymphoid tissue in lung transplantation: a facilitator of rejection or regulator of tolerance?Frontiers in immunology · 2025Review
- Immunomodulation by allograft endothelial cells.Frontiers in transplantation · 2025Review
- Regulatory T cell therapy in lung transplantation: bridging the gap from bench to bedside.Frontiers in immunology · 2025Review
- High-dimensional flow cytometry reveals lymphocyte subset populations predictive of chronic lung allograft dysfunction.Clinical & translational immunology · 2025Article
- Graft protective effects and donor-specific antibody suppression by CD4Journal of cardiothoracic surgery · 2024Article
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Antibody-mediated rejection (AMR) is a principal cause of acute and chronic failure of lung allografts. However, mechanisms mediating this oftentimes fatal complication are poorly understood. Here, we show that Foxp3+ T cells formed aggregates in rejection-free human lung grafts and accumulated within induced bronchus-associated lymphoid tissue (BALT) of tolerant mouse lungs. Using a retransplantation model, we show that selective depletion of graft-resident Foxp3+ T lymphocytes resulted in the generation of donor-specific antibodies (DSA) and AMR, which was associated with complement deposition and destruction of airway epithelium. AMR was dependent on graft infiltration by B and T cells. Depletion of graft-resident Foxp3+ T lymphocytes resulted in prolonged interactions between B and CD4+ T cells within transplanted lungs, which was dependent on CXCR5-CXCL13. Blockade of CXCL13 as well as inhibition of the CD40 ligand and the ICOS ligand suppressed DSA production and prevented AMR. Thus, we have shown that regulatory Foxp3+ T cells residing within BALT of tolerant pulmonary allografts function to suppress B cell activation, a finding that challenges the prevailing view that regulation of humoral responses occurs peripherally. As pulmonary AMR is largely refractory to current immunosuppression, our findings provide a platform for developing therapies that target local immune responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.